TY  - JOUR
AB  - Two articles in Immunity and Cancer Cell describe that bladder cancer immunotherapy with Bacillus Calmette-Guerin (BCG) alone or in combination with β-glucan, another agonist of trained immunity (TRIM), involves reprogramming of bone marrow (BM) hematopoiesis. These findings provide additional evidence of the therapeutic potential of BM-mediated TRIM against cancer.
AU  - Chronopoulos, J.*
AU  - Crespo, M.
AU  - Chavakis, T.
C1  - 75076
C2  - 57910
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 1394-1396
TI  - Central trained immunity in the context of bladder cancer immunotherapy.
JO  - Cancer Cell
VL  - 43
IS  - 8
PB  - Cell Press
PY  - 2025
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Epithelial serous borderline tumors (SBT) are non-invasive neoplastic ovarian lesions that may recur as chemo-resistant low-grade serous cancer (LGSC). While genetic alterations suggest a common origin, the transition from SBT to LGSC remains poorly understood. Here, we integrate cell-type resolved spatial proteomics and transcriptomics to elucidate the evolution from SBT to LGSC and its corresponding metastases in both stroma and tumor. The transition occurs within the epithelial compartment through an intermediary stage with micropapillary features, during which LGSC overexpresses c-Met and several brain-specific proteins. Within the tumor microenvironment, interconnectivity between cancer and stromal cells, along with enzymes degrading a packed extracellular matrix, suggests functional collaboration among various cell types. We functionally validated 16 drug targets identified through integrated spatial transcriptomics and proteomics. Combined treatment targeting CDK4/6 (milciclib) and FOLR1 (mirvetuximab) achieved significant tumor reduction in vivo, representing a promising therapeutic strategy for LGSC.
AU  - Schweizer, L.*
AU  - Kenny, H.A.*
AU  - Krishnan, R.*
AU  - Kelliher, L.*
AU  - Bilecz, A.J.*
AU  - Heide, J.*
AU  - Donle, L.*
AU  - Shimizu, A.*
AU  - Metousis, A.*
AU  - Mendoza, R.*
AU  - Nordmann, T.M.*
AU  - Rauch, S.*
AU  - Richter, S.
AU  - Li, Y.*
AU  - Rosenberger, F.A.*
AU  - Strauss, M.T.*
AU  - Kurnit, K.C.*
AU  - Thielert, M.*
AU  - Rodriguez, E.*
AU  - Müller-Reif, J.B.*
AU  - Yamada, S.D.*
AU  - Theis, F.J.
AU  - Mund, A.*
AU  - Lastra, R.R.*
AU  - Mann, M.*
AU  - Lengyel, E.*
C1  - 75038
C2  - 57729
TI  - Spatial proteo-transcriptomic profiling reveals the molecular landscape of borderline ovarian tumors and their invasive progression.
JO  - Cancer Cell
PY  - 2025
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Despite the improvement, approximately 60% of patients with relapsed or refractory (r/r) aggressive B cell lymphoma (B-NHL) do not achieve durable benefit from CAR-T cell therapy. To elucidate factors associated with CAR-T therapy resistance, we conducted high-dimensional analyses of pre- and post-CAR-T cell specimens. In patients with non-durable response, we identified a prognostically relevant lymphoma-associated myeloid-monocytic (LAMM) gene signature. In-depth profiling revealed a distinct CSF1R+CD14+CD68+ LAMM cell population in both human and murine B-NHL that inhibits CAR-T cell function and correlates with poor outcome. Cell-cell inference analysis uncovered that LAMM cells impair CAR-T cell function through a direct LAMM-T cell interaction via the PGE2-EP2/EP4 axis. In an autochthonous lymphoma mouse model, combined anti-CD19 CAR-T cell therapy with CSF1R blockade exhibited synergistic effects and improved survival. These findings provide strong rationale for combining anti-CD19 CAR-T cells with CSF1R inhibitors in treating r/r aggressive B-NHL patients.
AU  - Stahl, D.*
AU  - Gödel, P.*
AU  - Balke-Want, H.*
AU  - Gholamipoorfard, R.*
AU  - Segbers, P.*
AU  - Tetenborg, L.*
AU  - Koker, M.*
AU  - Dörr, J.*
AU  - Gregor, L.*
AU  - Bachurski, D.*
AU  - Rose, F.*
AU  - Simon, A.G.*
AU  - Good, Z.*
AU  - Jakob, J.*
AU  - Häupl, B.*
AU  - Nill, M.*
AU  - Flümann, R.*
AU  - Riet, T.*
AU  - Lange, D.*
AU  - Blakemore, S.J.*
AU  - Baurmann, H.*
AU  - Voltin, C.A.*
AU  - Potter, N.*
AU  - Schlözer, L.*
AU  - Freihammer, M.*
AU  - Wagener-Ryczek, S.*
AU  - Iuga, A.I.*
AU  - Heger, J.M.*
AU  - Ludwig, H.*
AU  - Schleifenbaum, J.K.*
AU  - Propp, J.*
AU  - Bröckelmann, P.J.*
AU  - Jachimowicz, R.D.*
AU  - Knittel, G.*
AU  - Borchmann, S.*
AU  - Merkelbach-Bruse, S.*
AU  - Pallasch, C.P.*
AU  - Peifer, M.*
AU  - Rybniker, J.*
AU  - Quaas, A.*
AU  - Nitz, M.*
AU  - Brägelmann, J.*
AU  - Müller, W.*
AU  - Persigehl, T.*
AU  - Bozek, K.*
AU  - Theobald, S.J.*
AU  - Büttner, R.*
AU  - Oellerich, T.*
AU  - Hallek, M.*
AU  - Kobold, S.
AU  - Chmielewski, M.*
AU  - Reinhardt, H.C.*
AU  - Mackall, C.*
AU  - Abedpour, N.*
AU  - Borchmann, P.*
AU  - Ullrich, R.T.*
C1  - 74929
C2  - 57749
TI  - CSF1R+ myeloid-monocytic cells drive CAR-T cell resistance in aggressive B cell lymphoma.
JO  - Cancer Cell
PY  - 2025
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Deep learning (DL) can accelerate the prediction of prognostic biomarkers from routine pathology slides in colorectal cancer (CRC). However, current approaches rely on convolutional neural networks (CNNs) and have mostly been validated on small patient cohorts. Here, we develop a new transformer-based pipeline for end-to-end biomarker prediction from pathology slides by combining a pre-trained transformer encoder with a transformer network for patch aggregation. Our transformer-based approach substantially improves the performance, generalizability, data efficiency, and interpretability as compared with current state-of-the-art algorithms. After training and evaluating on a large multicenter cohort of over 13,000 patients from 16 colorectal cancer cohorts, we achieve a sensitivity of 0.99 with a negative predictive value of over 0.99 for prediction of microsatellite instability (MSI) on surgical resection specimens. We demonstrate that resection specimen-only training reaches clinical-grade performance on endoscopic biopsy tissue, solving a long-standing diagnostic problem.
AU  - Wagner, S.
AU  - Reisenbüchler, D.
AU  - West, N.P.*
AU  - Niehues, J.M.*
AU  - Zhu, J.*
AU  - Foersch, S.*
AU  - Veldhuizen, G.P.*
AU  - Quirke, P.*
AU  - Grabsch, H.I.*
AU  - van den Brandt, P.A.*
AU  - Hutchins, G.G.A.*
AU  - Richman, S.D.*
AU  - Yuan, T.*
AU  - Langer, R.*
AU  - Jenniskens, J.C.A.*
AU  - Offermans, K.*
AU  - Mueller, W.*
AU  - Gray, R.*
AU  - Gruber, S.B.*
AU  - Greenson, J.K.*
AU  - Rennert, G.*
AU  - Bonner, J.D.*
AU  - Schmolze, D.*
AU  - Jonnagaddala, J.*
AU  - Hawkins, N.J.*
AU  - Ward, R.L.*
AU  - Morton, D.*
AU  - Seymour, M.*
AU  - Magill, L.*
AU  - Nowak, M.*
AU  - Hay, J.*
AU  - Koelzer, V.H.*
AU  - Church, D.N.*
AU  - Church, D.*
AU  - Domingo, E.*
AU  - Edwards, J.*
AU  - Glimelius, B.*
AU  - Gogenur, I.*
AU  - Harkin, A.*
AU  - Iveson, T.*
AU  - Jaeger, E.*
AU  - Kelly, C.*
AU  - Kerr, R.*
AU  - Maka, N.*
AU  - Morgan, H.*
AU  - Oien, K.*
AU  - Orange, C.*
AU  - Palles, C.*
AU  - Roxburgh, C.*
AU  - Sansom, O.*
AU  - Saunders, M.*
AU  - Tomlinson, I.*
AU  - Matek, C.
AU  - Geppert, C.*
AU  - Peng, C.*
AU  - Zhi, C.*
AU  - Ouyang, X.*
AU  - James, J.A.*
AU  - Loughrey, M.B.*
AU  - Salto-Tellez, M.*
AU  - Brenner, H.*
AU  - Hoffmeister, M.*
AU  - Truhn, D.*
AU  - Schnabel, J.A.
AU  - Boxberg, M.*
AU  - Peng, T.
AU  - Kather, J.N.*
C1  - 68336
C2  - 54758
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 1650-1661.e4
TI  - Transformer-based biomarker prediction from colorectal cancer histology: A large-scale multicentric study.
JO  - Cancer Cell
VL  - 41
IS  - 9
PB  - Cell Press
PY  - 2023
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Glioblastomas are malignant tumors of the central nervous system hallmarked by subclonal diversity and dynamic adaptation amid developmental hierarchies. The source of dynamic reorganization within the spatial context of these tumors remains elusive. Here, we characterized glioblastomas by spatially resolved transcriptomics, metabolomics, and proteomics. By deciphering regionally shared transcriptional programs across patients, we infer that glioblastoma is organized by spatial segregation of lineage states and adapts to inflammatory and/or metabolic stimuli, reminiscent of the reactive transformation in mature astrocytes. Integration of metabolic imaging and imaging mass cytometry uncovered locoregional tumor-host interdependence, resulting in spatially exclusive adaptive transcriptional programs. Inferring copy-number alterations emphasizes a spatially cohesive organization of subclones associated with reactive transcriptional programs, confirming that environmental stress gives rise to selection pressure. A model of glioblastoma stem cells implanted into human and rodent neocortical tissue mimicking various environments confirmed that transcriptional states originate from dynamic adaptation to various environments.
AU  - Ravi, V.M.*
AU  - Will, P.*
AU  - Kueckelhaus, J.*
AU  - Sun, N.
AU  - Joseph, K.*
AU  - Salié, H.*
AU  - Vollmer, L.*
AU  - Kuliesiute, U.*
AU  - von Ehr, J.*
AU  - Benotmane, J.K.*
AU  - Neidert, N.*
AU  - Follo, M.*
AU  - Scherer, F.*
AU  - Goeldner, J.M.*
AU  - Behringer, S.P.*
AU  - Franco, P.*
AU  - Khiat, M.*
AU  - Zhang, J.*
AU  - Hofmann, U.G.*
AU  - Fung, C.*
AU  - Ricklefs, F.L.*
AU  - Lamszus, K.*
AU  - Boerries, M.*
AU  - Ku, M.C.*
AU  - Beck, J.*
AU  - Sankowski, R.*
AU  - Schwabenland, M.*
AU  - Prinz, M.*
AU  - Schüller, U.*
AU  - Killmer, S.*
AU  - Bengsch, B.*
AU  - Walch, A.K.
AU  - Delev, D.*
AU  - Schnell, O.*
AU  - Heiland, D.H.*
C1  - 65389
C2  - 52291
SP  - 639-655.e13
TI  - Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma.
JO  - Cancer Cell
VL  - 40
IS  - 6
PY  - 2022
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Signals driving aberrant self-renewal in the heterogeneous leukemia stem cell (LSC) pool determine aggressiveness of acute myeloid leukemia (AML). We report that a positive modulator of canonical WNT signaling pathway, RSPO-LGR4, upregulates key self-renewal genes and is essential for LSC self-renewal in a subset of AML. RSPO2/3 serve as stem cell growth factors to block differentiation and promote proliferation of primary AML patient blasts. RSPO receptor, LGR4, is epigenetically upregulated and works through cooperation with HOXA9, a poor prognostic predictor. Blocking the RSPO3-LGR4 interaction by clinical-grade antiRSPO3 antibody (OMP-131R10/rosmantuzumab) impairs self-renewal and induces differentiation in AML patient-derived xenografts but does not affect normal hematopoietic stem cells, providing a therapeutic opportunity for HOXA9-dependent leukemia.
AU  - Salik, B.*
AU  - Yi, H.*
AU  - Hassan, N.*
AU  - Santiappillai, N.*
AU  - Vick, B.
AU  - Connerty, P.*
AU  - Duly, A.*
AU  - Trahair, T.*
AU  - Woo, A.J.*
AU  - Beck, D.*
AU  - Liu, T.*
AU  - Spiekermann, K.*
AU  - Jeremias, I.
AU  - Wang, J.*
AU  - Kavallaris, M.*
AU  - Haber, M.*
AU  - Norris, M.D.*
AU  - Liebermann, D.A.*
AU  - D'Andrea, R.J.*
AU  - Murriel, C.*
AU  - Wang, J.Y.*
C1  - 59511
C2  - 48888
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 263-278.e6
TI  - Targeting RSPO3-LGR4 signaling for leukemia stem cell eradication in acute myeloid leukemia.
JO  - Cancer Cell
VL  - 38
IS  - 2
PB  - Cell Press
PY  - 2020
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - How lymphoma cells (LCs) invade the brain during the development of central nervous system lymphoma (CNSL) is unclear. We found that NF-κB-induced gliosis promotes CNSL in immunocompetent mice. Gliosis elevated cell-adhesion molecules, which increased LCs in the brain but was insufficient to induce CNSL. Astrocyte-derived CCL19 was required for gliosis-induced CNSL. Deleting CCL19 in mice or CCR7 from LCs abrogated CNSL development. Two-photon microscopy revealed LCs transiently entering normal brain parenchyma. Astrocytic CCL19 enhanced parenchymal CNS retention of LCs, thereby promoting CNSL formation. Aged, gliotic wild-type mice were more susceptible to forming CNSL than young wild-type mice, and astrocytic CCL19 was observed in both human gliosis and CNSL. Therefore, CCL19-CCR7 interactions may underlie an increased age-related risk for CNSL.
AU  - O'Connor, T.
AU  - Zhou, X.*
AU  - Kosla, J.
AU  - Adili, A.
AU  - Garcia Beccaria, M.*
AU  - Kotsiliti, E.
AU  - Pfister, D.
AU  - Johlke, A.-L.
AU  - Sinha, A.*
AU  - Sankowski, R.*
AU  - Schick, M.*
AU  - Lewis, R.*
AU  - Dokalis, N.*
AU  - Seubert, B.
AU  - Höchst, B.*
AU  - Inverso, D.*
AU  - Heide, D.*
AU  - Zhang, W.*
AU  - Weihrich, P.*
AU  - Manske, K.*
AU  - Wohlleber, D.*
AU  - Anton, M.*
AU  - Hoellein, A.*
AU  - Seleznik, G.M.*
AU  - Bremer, J.*
AU  - Bleul, S.*
AU  - Augustin, H.G.*
AU  - Scherer, F.*
AU  - Koedel, U.*
AU  - Weber, A.*
AU  - Protzer, U.
AU  - Förster, R.*
AU  - Wirth, T.*
AU  - Aguzzi, A.*
AU  - Meissner, F.*
AU  - Prinz, M.*
AU  - Baumann, B.*
AU  - Höpken, U.E.*
AU  - Knolle, P.A.*
AU  - von Baumgarten, L.*
AU  - Keller, U.*
AU  - Heikenwälder, M.
C1  - 56843
C2  - 47400
SP  - 250-267.e9
TI  - Age-related gliosis promotes central nervous system lymphoma through CCL19-mediated tumor cell retention.
JO  - Cancer Cell
VL  - 36
IS  - 3
PY  - 2019
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Obesity is a leading risk factor for cancer. However, understanding the crosstalk between adipocytes and tumor cells in vivo, independently of dietary contributions, is a major gap in the field. Here we used a prostate cancer (PCa) mouse model in which the signaling adaptor p62/Sqstm1 is selectively inactivated in adipocytes. p62 loss in adipocytes results in increased osteopontin secretion, which mediates tumor fatty acid oxidation and invasion, leading to aggressive metastatic PCa in vivo. Furthermore, p62 deficiency triggers in adipocytes a general shutdown of energy-utilizing pathways through mTORC1 inhibition, which supports nutrient availability for cancer cells. This reveals a central role of adipocyte's p62 in the symbiotic adipose tissue-tumor collaboration that enables cancer metabolic fitness.
AU  - Huang, J.*
AU  - Duran, A.*
AU  - Reina-Campos, M.*
AU  - Valencia, T.*
AU  - Castilla, E.A.*
AU  - Müller, T.D.
AU  - Tschöp, M.H.
AU  - Moscat, J.*
AU  - Diaz-Meco, M.T.*
C1  - 53300
C2  - 44664
SP  - 770-784.e6
TI  - Adipocyte p62/SQSTM1 suppresses tumorigenesis through opposite regulations of metabolism in adipose tissue and tumor.
JO  - Cancer Cell
VL  - 33
IS  - 4
PY  - 2018
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis. Proliferation-associated DNA damage is sensed by a complex comprising caspase-8, FADD, c-FLIP, and a kinase-dependent function of RIPK1. This platform requires a non-apoptotic function of caspase-8, but no caspase-3 or caspase-8 cleavage. It may represent a DNA damage-sensing mechanism in hepatocytes that can act via JNK and subsequent phosphorylation of the histone variant H2AX.
AU  - Boege, Y.*
AU  - Malehmir, M.*
AU  - Healy, M.E.*
AU  - Bettermann, K.*
AU  - Lorentzen, A.R.
AU  - Vucur, M.*
AU  - Ahuja, A.K.*
AU  - Böhm, F.*
AU  - Mertens, J.C.*
AU  - Shimizu, Y.*
AU  - Frick, L.*
AU  - Remouchamps, C.*
AU  - Mutreja, K.*
AU  - Kähne, T.*
AU  - Sundaravinayagam, D.*
AU  - Wolf, M.J.*
AU  - Rehrauer, H.*
AU  - Koppe, C.*
AU  - Speicher, T.*
AU  - Padrissa-Altés, S.*
AU  - Maire, R.*
AU  - Schattenberg, J.M.*
AU  - Jeong, J.S.*
AU  - Liu, L.*
AU  - Zwirner, S.*
AU  - Boger, R.H.*
AU  - Hüser, N.*
AU  - Davis, R.J.*
AU  - Müllhaupt, B.*
AU  - Moch, H.*
AU  - Schulze-Bergkamen, H.*
AU  - Clavien, P.A.*
AU  - Werner, S.*
AU  - Borsig, L.*
AU  - Luther, S.A.*
AU  - Jost, P.J.*
AU  - Weinlich, R.*
AU  - Unger, K.
AU  - Behrens, A.*
AU  - Hillert, L.*
AU  - Dillon, C.*
AU  - Di Virgilio, M.*
AU  - Wallach, D.*
AU  - Dejardin, E.*
AU  - Zender, L.*
AU  - Naumann, M.*
AU  - Walczak, H.*
AU  - Green, D.R.*
AU  - Lopes, M.*
AU  - Lavrik, I.N.*
AU  - Luedde, T.*
AU  - Heikenwälder, M.
AU  - Weber, A.*
C1  - 51855
C2  - 43527
CY  - Cambridge
SP  - 342-359.e10
TI  - A dual role of caspase-8 in triggering and sensing proliferation-associated DNA damage, a key determinant of liver cancer development.
JO  - Cancer Cell
VL  - 32
IS  - 3
PB  - Cell Press
PY  - 2017
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Intrahepatic cholangiocarcinoma (ICC) is a highly malignant, heterogeneous cancer with poor treatment options. We found that mitochondrial dysfunction and oxidative stress trigger a niche favoring cholangiocellular overgrowth and tumorigenesis. Liver damage, reactive oxygen species (ROS) and paracrine tumor necrosis factor (Tnf) from Kupffer cells caused JNK-mediated cholangiocellular proliferation and oncogenic transformation. Anti-oxidant treatment, Kupffer cell depletion, Tnfr1 deletion, or JNK inhibition reduced cholangiocellular pre-neoplastic lesions. Liver-specific JNK1/2 deletion led to tumor reduction and enhanced survival in Akt/Notch- or p53/Kras-induced ICC models. In human ICC, high Tnf expression near ICC lesions, cholangiocellular JNK-phosphorylation, and ROS accumulation in surrounding hepatocytes are present. Thus, Kupffer cell-derived Tnf favors cholangiocellular proliferation/differentiation and carcinogenesis. Targeting the ROS/Tnf/JNK axis may provide opportunities for ICC therapy.
AU  - Yuan, D.T.
AU  - Ringelhan, M.
AU  - Connor, T.O.
AU  - Simonavicius, N.
AU  - Reisinger, F.
AU  - Leone, V.
AU  - Protzer, U.
AU  - Unger, K.
AU  - Heikenwälder, M.
C1  - 51302
C2  - 42987
SP  - 771-789.e6
TI  - Kupffer cell-derived Tnf triggers cholangiocellular tumorigenesis through JNK due to chronic mitochondrial dysfunction and ROS.
JO  - Cancer Cell
VL  - 31
IS  - 6
PY  - 2017
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Tumor relapse is associated with dismal prognosis, but responsible biological principles remain incompletely understood. To isolate and characterize relapse-inducing cells, we used genetic engineering and proliferation-sensitive dyes in patient-derived xenografts of acute lymphoblastic leukemia (ALL). We identified a rare subpopulation that resembled relapse-inducing cells with combined properties of long-term dormancy, treatment resistance, and stemness. Single-cell and bulk expression profiling revealed their similarity to primary ALL cells isolated from pediatric and adult patients at minimal residual disease (MRD). Therapeutically adverse characteristics were reversible, as resistant, dormant cells became sensitive to treatment and started proliferating when dissociated from the in vivo environment. Our data suggest that ALL patients might profit from therapeutic strategies that release MRD cells from the niche.
AU  - Ebinger, S.
AU  - Özdemir, E.Z.
AU  - Ziegenhain, C.*
AU  - Tiedt, S.
AU  - Castro Alves, C.
AU  - Grunert, M.
AU  - Dworzak, M.*
AU  - Lutz, C.*
AU  - Turati, V.A.*
AU  - Enver, T.*
AU  - Horny, H.-P.*
AU  - Sotlar, K.*
AU  - Parekh, S.*
AU  - Spiekermann, K.*
AU  - Hiddemann, W.*
AU  - Schepers, A.
AU  - Polzer, B.*
AU  - Kirsch, S.*
AU  - Hoffmann, M.*
AU  - Knapp, B.
AU  - Hasenauer, J.
AU  - Pfeifer, H.*
AU  - Panzer-Grümayer, R.*
AU  - Enard, W.*
AU  - Gires, O.*
AU  - Jeremias, I.
C1  - 50163
C2  - 42019
CY  - Cambridge
SP  - 849-862
TI  - Characterization of rare, dormant, and therapy-resistant cells in acute lymphoblastic leukemia.
JO  - Cancer Cell
VL  - 30
IS  - 6
PB  - Cell Press
PY  - 2016
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Oncogene-induced senescence causes hepatocytes to secrete cytokines, which induce their immune-mediated clearance to prevent tumor initiation, a process termed "senescence surveillance." However, senescent hepatocytes give rise to hepatocellular carcinomas (HCCs), if the senescence program is bypassed or if senescent cells are not cleared. Here, we show context-specific roles for CCR2(+) myeloid cells in liver cancer. Senescence surveillance requires the recruitment and maturation of CCR2(+) myeloid cells, and CCR2 ablation caused outgrowth of HCC. In contrast, HCC cells block the maturation of recruited myeloid precursors, which, through NK cell inhibition, promote growth of murine HCC and worsen the prognosis and survival of human HCC patients. Thus, while senescent hepatocyte-secreted chemokines suppress liver cancer initiation, they may accelerate the growth of fully established HCC.
AU  - Eggert, T.*
AU  - Wolter, K.*
AU  - Ji, J.*
AU  - Ma, C.*
AU  - Yevsa, T.*
AU  - Klotz, S.*
AU  - Medina-Echeverz, J.*
AU  - Longerich, T.*
AU  - Forgues, M.*
AU  - Reisinger, F.
AU  - Heikenwälder, M.
AU  - Wang, X.W.*
AU  - Zender, L.*
AU  - Greten, T.F.*
C1  - 49707
C2  - 40880
CY  - Cambridge
SP  - 533-547
TI  - Distinct functions of senescence-associated immune responses in liver tumor surveillance and tumor progression.
JO  - Cancer Cell
VL  - 30
IS  - 4
PB  - Cell Press
PY  - 2016
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Hepatocellular carcinoma (HCC) represents a classic example of inflammation-linked cancer. To characterize the role of the immune system in hepatic injury and tumor development, we comparatively studied the extent of liver disease and hepatocarcinogenesis in immunocompromised versus immunocompetent Fah-deficient mice. Strikingly, chronic liver injury and tumor development were markedly suppressed in alymphoid Fah(-/-) mice despite an overall increased mortality. Mechanistically, we show that CD8(+) T cells and lymphotoxin β are central mediators of HCC formation. Antibody-mediated depletion of CD8(+) T cells as well as pharmacological inhibition of the lymphotoxin-β receptor markedly delays tumor development in mice with chronic liver injury. Thus, our study unveils distinct functions of the immune system, which are required for liver regeneration, survival, and hepatocarcinogenesis.
AU  - Endig, J.*
AU  - Buitrago-Molina, L.E.*
AU  - Marhenke, S.*
AU  - Reisinger, F.
AU  - Saborowski, A.*
AU  - Schütt, J.*
AU  - Limbourg, F.*
AU  - Könecke, C.*
AU  - Schreder, A.*
AU  - Michael, A.*
AU  - Misslitz, A.C.*
AU  - Healy, M.E.*
AU  - Geffers, R.*
AU  - Clavel, T.*
AU  - Haller, D.*
AU  - Unger, K.
AU  - Finegold, M.*
AU  - Weber, A.*
AU  - Manns, M.P.*
AU  - Longerich, T.*
AU  - Heikenwälder, M.*
AU  - Vogel, A.*
C1  - 49209
C2  - 40691
CY  - Cambridge
SP  - 308-323
TI  - Dual role of the adaptive immune system in liver injury and hepatocellular carcinoma development.
JO  - Cancer Cell
VL  - 30
IS  - 8
PB  - Cell Press
PY  - 2016
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Since acute myeloid leukemia (AML) is characterized by the blockade of hematopoietic differentiation and cell death, we interrogated RIPK3 signaling in AML development. Genetic loss of Ripk3 converted murine FLT3-ITD-driven myeloproliferation into an overt AML by enhancing the accumulation of leukemia-initiating cells (LIC). Failed inflammasome activation and cell death mediated by tumor necrosis factor receptor caused this accumulation of LIC exemplified by accelerated leukemia onset in Il1r1(-/-), Pycard(-/-), and Tnfr1/2(-/-) mice. RIPK3 signaling was partly mediated by mixed lineage kinase domain-like. This link between suppression of RIPK3, failed interleukin-1β release, and blocked cell death was supported by significantly reduced RIPK3 in primary AML patient cohorts. Our data identify RIPK3 and the inflammasome as key tumor suppressors in AML.
AU  - Höckendorf, U.*
AU  - Yabal, M.*
AU  - Herold, T.*
AU  - Munkhbaatar, E.*
AU  - Rott, S.*
AU  - Jilg, S.*
AU  - Kauschinger, J.*
AU  - Magnani, G.*
AU  - Reisinger, F.
AU  - Heuser, M.*
AU  - Kreipe, H.*
AU  - Sotlar, K.*
AU  - Engleitner, T.*
AU  - Rad, R.*
AU  - Weichert, W.*
AU  - Peschel, C.*
AU  - Ruland, J.*
AU  - Heikenwälder, M.
AU  - Spiekermann, K.*
AU  - Slotta-Huspenina, J.*
AU  - Groß, O.*
AU  - Jost, P.J.*
C1  - 49088
C2  - 41645
CY  - Cambridge
SP  - 75-91
TI  - RIPK3 restricts myeloid leukemogenesis by promoting cell death and differentiation of leukemia initiating cells.
JO  - Cancer Cell
VL  - 30
IS  - 1
PB  - Cell Press
PY  - 2016
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease.
AU  - Townsend, E.C.*
AU  - Murakami, M.A.*
AU  - Christodoulou, A.N.*
AU  - Christie, A.L.*
AU  - Koster, J.*
AU  - DeSouza, T.A.*
AU  - Morgan, E.A.*
AU  - Kallgren, S.P.*
AU  - Liu, H.*
AU  - Wu, S.C.*
AU  - Plana, O.*
AU  - Montero, J.*
AU  - Stevenson, K.E.*
AU  - Rao, P.*
AU  - Vadhi, R.*
AU  - Andreeff, M.*
AU  - Armand, P.*
AU  - Ballen, K.K.*
AU  - Barzaghi-Rinaudo, P.*
AU  - Cahill, S.*
AU  - Clark, R.A.*
AU  - Cooke, V.G.*
AU  - Davids, M.S.*
AU  - DeAngelo, D.J.*
AU  - Dorfman, D.M.*
AU  - Eaton, H.*
AU  - Ebert, B.L.*
AU  - Etchin, J.*
AU  - Firestone, B.*
AU  - Fisher, D.C.*
AU  - Freedman, A.S.*
AU  - Galinsky, I.A.*
AU  - Gao, H.*
AU  - Garcia, J.S.*
AU  - Garnache-Ottou, F.*
AU  - Graubert, T.A.*
AU  - Gutierrez, A.*
AU  - Halilovic, E.*
AU  - Harris, M.H.*
AU  - Herbert, Z.T.*
AU  - Horwitz, S.M.*
AU  - Inghirami, G.*
AU  - Intlekoffer, A.M.*
AU  - Ito, M.*
AU  - Izraeli, S.*
AU  - Jacobsen, E.D.*
AU  - Jacobson, C.A.*
AU  - Jeay, S.*
AU  - Jeremias, I.
AU  - Kelliher, M.A.*
AU  - Koch, R.*
AU  - Konopleva, M.*
AU  - Kopp, N.*
AU  - Kornblau, S.M.*
AU  - Kung, A.L.*
AU  - Kupper, T.S.*
AU  - LaBoeuf, N.*
AU  - LaCasce, A.S.*
AU  - Lees, E.*
AU  - Li, L.S.*
AU  - Look, A.T.*
AU  - Murakami, M.*
AU  - Muschen, M.*
AU  - Neuberg, D.*
AU  - Ng, S.Y.*
AU  - Odejide, O.O.*
AU  - Orkin, S.H.*
AU  - Paquette, R.R.*
AU  - Place, A.E.*
AU  - Roderick, J.E.*
AU  - Ryan, J.A.*
AU  - Sallan, S.E.*
AU  - Shoji, B.*
AU  - Silverman, L.B.*
AU  - Soiffer, R.J.*
AU  - Steensma, D.P.*
AU  - Stegmaier, K.*
AU  - Stone, R.M.*
AU  - Tamburini, J.*
AU  - Thorner, A.R.*
AU  - van Hummelen, P.*
AU  - Wadleigh, M.*
AU  - Wiesmann, M.*
AU  - Weng, A.P.*
AU  - Wuerthner, J.U.*
AU  - Williams, D.A.*
AU  - Wollison, B.M.*
AU  - Lane, A.A.*
AU  - Letai, A.G.*
AU  - Bertagnolli, M.M.*
AU  - Ritz, J.*
AU  - Brown, M.*
AU  - Long, H.*
AU  - Aster, J.C.*
AU  - Shipp, M.A.*
AU  - Griffin, J.D.*
AU  - Weinstock, D.M.*
C1  - 48392
C2  - 41022
CY  - Cambridge
SP  - 574-586
TI  - The public repository of xenografts enables discovery and randomized phase II-like trials in mice.
JO  - Cancer Cell
VL  - 29
IS  - 4
PB  - Cell Press
PY  - 2016
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - How obesity and metabolic syndrome trigger non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remains elusive. In this issue, Gomes and colleagues describe that nutrient surplus induces hepatic URI expression, triggering genotoxicity and IL17A expression, thus leading to insulin resistance, NASH, and HCC. IL17A signaling blockers might become a readily translatable therapy.
AU  - Weber, A.*
AU  - Heikenwälder, M.
C1  - 49089
C2  - 41644
CY  - Cambridge
SP  - 15-17
TI  - P(URI)fying novel drivers of NASH and HCC: A feedforward loop of IL17A via white adipose tissue.
JO  - Cancer Cell
VL  - 30
IS  - 1
PB  - Cell Press
PY  - 2016
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Hepatocellular carcinoma (HCC), the fastest rising cancer in the United States and increasing in Europe, often occurs with nonalcoholic steatohepatitis (NASH). Mechanisms underlying NASH and NASH-induced HCC are largely unknown. We developed a mouse model recapitulating key features of human metabolic syndrome, NASH, and HCC by long-term feeding of a choline-deficient high-fat diet. This induced activated intrahepatic CD8(+) T cells, NKT cells, and inflammatory cytokines, similar to NASH patients. CD8(+) T cells and NKT cells but not myeloid cells promote NASH and HCC through interactions with hepatocytes. NKT cells primarily cause steatosis via secreted LIGHT, while CD8(+) and NKT cells cooperatively induce liver damage. Hepatocellular LTβR and canonical NF-κB signaling facilitate NASH-to-HCC transition, demonstrating that distinct molecular mechanisms determine NASH and HCC development.
AU  - Wolf, M.J.*
AU  - Adili, A.
AU  - Piotrowitz, K.*
AU  - Abdullah, Z.*
AU  - Boege, Y.*
AU  - Stemmer, K.
AU  - Ringelhan, M.
AU  - Simonavicius, N.
AU  - Egger, M.*
AU  - Wohlleber, D.*
AU  - Lorentzen, A.R.
AU  - Einer, C.
AU  - Schulz, S.
AU  - Clavel, T.*
AU  - Protzer, U.
AU  - Thiele, C.*
AU  - Zischka, H.
AU  - Moch, H.*
AU  - Tschöp, M.H.
AU  - Tumanov, A.V.*
AU  - Haller, D.*
AU  - Unger, K.
AU  - Karin, M.*
AU  - Kopf, M.*
AU  - Knolle, P.*
AU  - Weber, A.*
AU  - Heikenwälder, M.
C1  - 32552
C2  - 35140
SP  - 549-564
TI  - Metabolic activation of intrahepatic CD8+ T cells and NKT cells causes nonalcoholic steatohepatitis and liver cancer via cross-talk with hepatocytes.
JO  - Cancer Cell
VL  - 26
IS  - 4
PY  - 2014
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Proteolytic activity of the mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1) paracaspase is required for survival of the activated B cell subtype of diffuse large B cell lymphoma (ABC-DLBCL). We have identified distinct derivatives of medicinal active phenothiazines, namely mepazine, thioridazine, and promazine, as small molecule inhibitors of the MALT1 protease. These phenothiazines selectively inhibit cleavage activity of recombinant and cellular MALT1 by a noncompetitive mechanism. Consequently, the compounds inhibit anti-apoptotic NF-κB signaling and elicit toxic effects selectively on MALT1-dependent ABC-DLBCL cells in vitro and in vivo. Our data provide a conceptual proof for a clinical application of distinct phenothiazines in the treatment of ABC-DLBCL.
AU  - Nagel, D.
AU  - Spranger, S.
AU  - Vincendeau, M.
AU  - Grau, M.*
AU  - Raffegerst, S.H.
AU  - Kloo, B.
AU  - Hlahla, D.
AU  - Neuenschwander, M.*
AU  - von Kries, J.P.*
AU  - Hadian, K.
AU  - Dörken, B.*
AU  - Lenz, P.*
AU  - Lenz, G.*
AU  - Schendel, D.J.
AU  - Krappmann, D.
C1  - 11612
C2  - 30715
SP  - 825-837
TI  - Pharmacologic inhibition of MALT1 protease by phenothiazines as a therapeutic approach for the treatment of aggressive ABC-DLBCL.
JO  - Cancer Cell
VL  - 22
IS  - 6
PB  - Cell Press
PY  - 2012
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Increased expression of the chemokine CCL2 in tumor cells correlates with enhanced metastasis, poor prognosis, and recruitment of CCR2(+)Ly6C(hi) monocytes. However, the mechanisms driving tumor cell extravasation through the endothelium remain elusive. Here, we describe CCL2 upregulation in metastatic UICC stage IV colon carcinomas and demonstrate that tumor cell-derived CCL2 activates the CCR2(+) endothelium to increase vascular permeability in vivo. CCR2 deficiency prevents colon carcinoma extravasation and metastasis. Of note, CCR2 expression on radio-resistant cells or endothelial CCR2 expression restores extravasation and metastasis in Ccr2(-/-) mice. Reduction of CCR2 expression on myeloid cells decreases but does not prevent metastasis. CCL2-induced vascular permeability and metastasis is dependent on JAK2-Stat5 and p38MAPK signaling. Our study identifies potential targets for treating CCL2-dependent metastasis.
AU  - Wolf, M.J.*
AU  - Hoos, A.*
AU  - Bauer, J.
AU  - Boettcher, S.*
AU  - Knust, M.*
AU  - Weber, A.*
AU  - Simonavicius, N.
AU  - Schneider, C.*
AU  - Lang, M.*
AU  - Stürzl, M.*
AU  - Croner, R.S.*
AU  - Konrad, A.*
AU  - Manz, M.G.*
AU  - Moch, H.*
AU  - Aguzzi, A.*
AU  - van Loo, G.*
AU  - Pasparakis, M.*
AU  - Prinz, M.*
AU  - Borsig, L.*
AU  - Heikenwälder, M.
C1  - 8301
C2  - 30109
SP  - 91-105
TI  - Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPK pathway.
JO  - Cancer Cell
VL  - 22
IS  - 1
PB  - Cell Press
PY  - 2012
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - The MAP3-kinase TGF-beta-activated kinase 1 (TAK1) critically modulates innate and adaptive immune responses and connects cytokine stimulation with activation of inflammatory signaling pathways. Here, we report that conditional ablation of TAK1 in liver parenchymal cells (hepatocytes and cholangiocytes) causes hepatocyte dysplasia and early-onset hepatocarcinogenesis, coinciding with biliary ductopenia and cholestasis. TAK1-mediated cancer suppression is exerted through activating NF-kappaB in response to tumor necrosis factor (TNF) and through preventing Caspase-3-dependent hepatocyte and cholangiocyte apoptosis. Moreover, TAK1 suppresses a procarcinogenic and pronecrotic pathway, which depends on NF-kappaB-independent functions of the I kappaB-kinase (IKK)-subunit NF-kappaB essential modulator (NEMO). Therefore, TAK1 serves as a gatekeeper for a protumorigenic, NF-kappaB-independent function of NEMO in parenchymal liver cells.
AU  - Bettermann, K.*
AU  - Vucur, M.*
AU  - Haybaeck, J.*
AU  - Koppe, C.*
AU  - Janssen, J.*
AU  - Heymann, F.*
AU  - Weber, A.*
AU  - Weiskirchen, R.*
AU  - Liedtke, C.*
AU  - Gassler, N.*
AU  - Müller, M.*
AU  - de Vos, R.*
AU  - Wolf, M.J.*
AU  - Boege, Y.*
AU  - Seleznik, G.M.*
AU  - Zeller, N.*
AU  - Erny, D.*
AU  - Fuchs, T.*
AU  - Zoller, S.*
AU  - Cairo, S.*
AU  - Buendia, M.A.*
AU  - Prinz, M.*
AU  - Akira, S.*
AU  - Tacke, F.*
AU  - Heikenwälder, M.
AU  - Trautwein, C.*
AU  - Luedde, T.*
C1  - 2095
C2  - 28338
SP  - 481-496
TI  - TAK1 suppresses a NEMO-dependent but NF-κB-independent pathway to liver cancer.
JO  - Cancer Cell
VL  - 17
IS  - 5
PB  - Elsevier
PY  - 2010
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Immune responses may arrest tumor growth by inducing tumor dormancy. The mechanisms leading to either tumor dormancy or promotion of multistage carcinogenesis by adaptive immunity are poorly characterized. Analyzing T antigen (Tag)-induced multistage carcinogenesis in pancreatic islets, we show that Tag-specific CD4+ T cells home selectively into the tumor microenvironment around the islets, where they either arrest or promote transition of dysplastic islets into islet carcinomas. Through combined TNFR1 signaling and IFN-gamma signaling, Tag-specific CD4+ T cells induce antiangiogenic chemokines and prevent alpha(v)beta(3) integrin expression, tumor angiogenesis, tumor cell proliferation, and multistage carcinogenesis, without destroying Tag-expressing islet cells. In the absence of either TNFR1 signaling or IFN-gamma signaling, the same T cells paradoxically promote angiogenesis and multistage carcinogenesis. Thus, tumor-specific T cells can directly survey multistage carcinogenesis through cytokine signaling.
AU  - Müller-Hermelink, N.*
AU  - Braumüller, H.*
AU  - Pichler, B.*
AU  - Wieder, T.*
AU  - Mailhammer, R.
AU  - Schaak, K.*
AU  - Ghoreschi, K.*
AU  - Yazdi, A.*
AU  - Haubner, R.*
AU  - Sander, CA.*
AU  - Mocikat, R.
AU  - Schwaiger, M.*
AU  - Förster, I.*
AU  - Huss, R.*
AU  - Weber, WA.*
AU  - Kneilling, M.*
AU  - Röcken, M.*
C1  - 4568
C2  - 25377
SP  - 507-518
TI  - TNFR1 signaling and IFN-gamma signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis.
JO  - Cancer Cell
VL  - 13
IS  - 6
PB  - Cell Press
PY  - 2008
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - A challenge for the development of therapies selectively targeting leukemic stem cells in acute myeloid leukemia (AML) is their similarity to normal hematopoietic stem cells (HSCs). Here we demonstrate that the leukemia-propagating cell in murine CALM/AF10-positive AML differs from normal HSCs by B220 surface expression and immunoglobulin heavy chain rearrangement. Furthermore, depletion of B220+ cells in leukemic transplants impaired development of leukemia in recipients. As in the murine model, human CALM/AF10-positive AML was characterized by CD45RA (B220)-positive, IG DH-JH rearranged leukemic cells. These data demonstrate in a murine leukemia model that AML can be propagated by a transformed progenitor with lymphoid characteristics, which can be targeted by antibodies that do not crossreact with normal HSCs. © 2006 Elsevier Inc. All rights reserved.
AU  - Deshpande, A.J.
AU  - Cusan, M.
AU  - Rawat, V.P.S.
AU  - Reuter, H.
AU  - Krause, A.
AU  - Pott, C.*
AU  - Quintanilla-Martinez, L.
AU  - Kakadia, P.
AU  - Kuchenbauer, F.
AU  - Ahmed, F.
AU  - Delabesse, E.*
AU  - Hahn, M.*
AU  - Lichtner, P.*
AU  - Kneba, M.
AU  - Hiddemann, W.
AU  - Macintyre, E.*
AU  - Mecucci, C.*
AU  - Ludwig, W.D.*
AU  - Humphries, R.K.*
AU  - Bohlander, S.K.
AU  - Feuring-Buske, M.
AU  - Buske, C.
C1  - 3991
C2  - 24082
SP  - 363-374
TI  - Acute myeloid leukemia is propagated by a leukemic stem cell with lymphoid characteristics in a mouse model of CALM/AF10-positive leukemia.
JO  - Cancer Cell
VL  - 10
IS  - 5
PY  - 2006
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - We show that mouse embryonic endothelial progenitor cells (eEPCs) home preferentially to hypoxic lung metastases when administered intravenously. This specificity is inversely related to the degree of perfusion and vascular density in the metastasis and directly related to local levels of hypoxia and VEGF. Ex vivo expanded eEPCs that were genetically modified with a suicide gene specifically and efficiently eradicated lung metastases with scant patent blood vessels. eEPCs do not express MHC I proteins, are resistant to natural killer cell-mediated cytolysis, and can contribute to tumor vessel formation also in nonsyngeneic mice. These results indicate that eEPCs can be used in an allogeneic setting to treat hypoxic metastases that are known to be resistant to conventional therapeutic regimes.
AU  - Wei, J.*
AU  - Blum, S.
AU  - Jarmy, G.*
AU  - Lamparter, M.
AU  - Geishauser, A.
AU  - Vlastos, G.A.
AU  - Chan, G.*
AU  - Fischer, K.-D.
AU  - Rattat, D.*
AU  - Debatin, K.-M.*
AU  - Hatzopoulos, A.K.
C1  - 3303
C2  - 21802
SP  - 477-488
TI  - Embryonic endothelial progenitor cells armed with a suicide gene target hypoxic lung metastasis after intravenous delivery.
JO  - Cancer Cell
VL  - 5
IS  - 5
PY  - 2004
SN  - 1535-6108
ER  - 

TY  - JOUR
AB  - Inappropriate transcriptional repression involving histone deacetylases (HDACs) is a prominent cause for the development of leukemia. We now identify faulty expression of a specific mediator of transcriptional repression in a solid tumor. Loss of the adenomatosis polyposis coli (APC) tumor suppressor induces HDAC2 expression depending on the Wnt pathway and c-Myc. Increased HDAC2 expression is found in the majority of human colon cancer explants, as well as in intestinal mucosa and polyps of APC-deficient mice. HDAC2 is required for, and sufficient on its own to prevent, apoptosis of colonic cancer cells. Interference with HDAC2 by valproic acid largely diminishes adenoma formation in APCmin mice. These findings point toward HDAC2 as a particularly relevant potential target in cancer therapy.
AU  - Zhu, P.*
AU  - Martin, E.*
AU  - Mengwasser, J.*
AU  - Schlag, P.*
AU  - Janssen, K.-P.*
AU  - Göttlicher, M.
C1  - 3344
C2  - 21807
SP  - 455-463
TI  - Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis.
JO  - Cancer Cell
VL  - 5
IS  - 5
PY  - 2004
SN  - 1535-6108
ER  -