TY - JOUR AB - Background Experimental mouse models are indispensable for the preclinical development of cancer immunotherapies, whereby complex interactions in the tumor microenvironment can be somewhat replicated. Despite the availability of diverse models, their predictive capacity for clinical outcomes remains largely unknown, posing a hurdle in the translation from preclinical to clinical success. Methods This study systematically reviews and meta-analyzes clinical trials of chimeric antigen receptor (CAR)-T cell monotherapies with their corresponding preclinical studies. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive search of PubMed and ClinicalTrials.gov was conducted, identifying 422 clinical trials and 3,157 preclinical studies. From these, 105 clinical trials and 180 preclinical studies, accounting for 44 and 131 distinct CAR constructs, respectively, were included. Results Patients' responses varied based on the target antigen, expectedly with higher efficacy and toxicity rates in hematological cancers. Preclinical data analysis revealed homogeneous and antigen-independent efficacy rates. Our analysis revealed that only 4% (n=12) of mouse studies used syngeneic models, highlighting their scarcity in research. Three logistic regression models were trained on CAR structures, tumor entities, and experimental settings to predict treatment outcomes. While the logistic regression model accurately predicted clinical outcomes based on clinical or preclinical features (Macro F1 and area under the curve (AUC)>0.8), it failed in predicting preclinical outcomes from preclinical features (Macro F1<0.5, AUC<0.6), indicating that preclinical studies may be influenced by experimental factors not accounted for in the model. Conclusion These findings underscore the need to better understand the experimental factors enhancing the predictive accuracy of mouse models in preclinical settings. AU - Andreu-Sanz, D.* AU - Gregor, L.* AU - Carlini, E.* AU - Scarcella, D. AU - Marr, C. AU - Kobold, S. C1 - 74928 C2 - 57654 CY - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England TI - Predictive value of preclinical models for CAR-T cell therapy clinical trials: A systematic review and meta-analysis. JO - J. Immunother. Cancer VL - 13 IS - 6 PB - Bmj Publishing Group PY - 2025 SN - 2051-1426 ER - TY - JOUR AB - BACKGROUND: Impairment of Akt signaling has been observed in antigen-specific cytotoxic T lymphocytes (CTLs) during chronic viral infections or tumor progression. Despite numerous studies emphasizing Akt's role in driving CTL effector functions, there is limited exploration of using Akt molecules in T-cell engineering to enhance their antiviral or antitumor capabilities for therapeutic purposes. Some studies even conclude that inhibiting Akt activation during the in vitro expansion process can prevent T-cell exhaustion and boost the antitumor effector functions of chimeric antigen receptor-T cells in vivo. Given the unique expression patterns and functions of the three Akt isoforms in immune cells, we proposed that Akt isoforms in CTLs may regulate effector functions and T-cell exhaustion distinctly. METHODS: In this study, we genetically modified tumor/virus-antigen-specific T-cell receptor tg CTLs to ectopically express Akt isoforms via retroviral transduction. We subsequently conducted western blotting, flow cytometry, and RNA sequencing analysis to assess their Akt expression, expression of immune checkpoints, antitumor/antivirus functionalities, and transcriptome. Additionally, we employed a persistent Hepatitis B Virus mouse model and a syngeneic hepatocellular carcinoma mouse model for further evaluation of their antivirus/antitumor efficacies. RESULTS: We found that both Akt1 and Akt2 overexpression enhanced the cytotoxic capabilities of mouse CTLs, although with different dynamics. Specifically, Akt2 signaling in CTLs accelerated effector functions, leading to a rapid attack on tumor cells. Conversely, Akt1 signaling triggered calcium influx and subsequent nuclear factor of activated T cells (NFAT) activation, while Akt2 signaling suppressed calcium influx, preventing excessive NFAT expression and nuclear translocation. This repression of NFAT transcriptional activity by Akt2 signaling during prolonged antigen stimulation subsequently led to reduced expression of transcription factors associated with T-cell exhaustion, such as Egr2, Nr4a, Tox, and immune checkpoints. Consequently, Akt2-overexpressed CTLs displayed reduced T-cell exhaustion within the tumor microenvironment and efficiently eradicated tumors. CONCLUSION: These findings highlight the essential role of Akt signaling in enabling tumor-specific CTLs to eliminate cancer cells in the solid TME, with Akt isoforms differentially regulating the calcium-calcineurin-NFAT signaling pathway. This discovery suggests the potential of AKT2 in T-cell engineering technology to enhance the survival and effector functions of adoptively transferred T cells for treating liver malignancies or chronic viral infections. AU - Chen, W.L.* AU - Chang, Y.L.* AU - Lin, S.F.* AU - Protzer, U. AU - Isogawa, M.* AU - Yang, H.C.* AU - Huang, L.R.* C1 - 73785 C2 - 57221 TI - Differential regulation of calcium-NFAT signaling pathway by Akt isoforms: Unraveling effector dynamics and exhaustion of cytotoxic T lymphocytes in tumor microenvironment. JO - J. Immunother. Cancer VL - 13 IS - 3 PY - 2025 SN - 2051-1426 ER - TY - JOUR AB - BACKGROUND: Melanoma is an immune sensitive disease, as demonstrated by the activity of immune check point blockade (ICB), but many patients will either not respond or relapse. More recently, tumor infiltrating lymphocyte (TIL) therapy has shown promising efficacy in melanoma treatment after ICB failure, indicating the potential of cellular therapies. However, TIL treatment comes with manufacturing limitations, product heterogeneity, as well as toxicity problems, due to the transfer of a large number of phenotypically diverse T cells. To overcome said limitations, we propose a controlled adoptive cell therapy approach, where T cells are armed with synthetic agonistic receptors (SAR) that are selectively activated by bispecific antibodies (BiAb) targeting SAR and melanoma-associated antigens. METHODS: Human as well as murine SAR constructs were generated and transduced into primary T cells. The approach was validated in murine, human and patient-derived cancer models expressing the melanoma-associated target antigens tyrosinase-related protein 1 (TYRP1) and melanoma-associated chondroitin sulfate proteoglycan (MCSP) (CSPG4). SAR T cells were functionally characterized by assessing their specific stimulation and proliferation, as well as their tumor-directed cytotoxicity, in vitro and in vivo. RESULTS: MCSP and TYRP1 expression was conserved in samples of patients with treated as well as untreated melanoma, supporting their use as melanoma-target antigens. The presence of target cells and anti-TYRP1 × anti-SAR or anti-MCSP × anti-SAR BiAb induced conditional antigen-dependent activation, proliferation of SAR T cells and targeted tumor cell lysis in all tested models. In vivo, antitumoral activity and long-term survival was mediated by the co-administration of SAR T cells and BiAb in a syngeneic tumor model and was further validated in several xenograft models, including a patient-derived xenograft model. CONCLUSION: The SAR T cell-BiAb approach delivers specific and conditional T cell activation as well as targeted tumor cell lysis in melanoma models. Modularity is a key feature for targeting melanoma and is fundamental towards personalized immunotherapies encompassing cancer heterogeneity. Because antigen expression may vary in primary melanoma tissues, we propose that a dual approach targeting two tumor-associated antigens, either simultaneously or sequentially, could avoid issues of antigen heterogeneity and deliver therapeutic benefit to patients. AU - Märkl, F.* AU - Benmebarek, M.R.* AU - Keyl, J.* AU - Cadilha, B.L.* AU - Geiger, M.* AU - Karches, C.* AU - Obeck, H.* AU - Schwerdtfeger, M.* AU - Michaelides, S.* AU - Briukhovetska, D.* AU - Stock, S.* AU - Jobst, J.* AU - Müller, P.J.* AU - Majed, L.* AU - Seifert, M.* AU - Klüver, A.K.* AU - Lorenzini, T.* AU - Grünmeier, R.* AU - Thomas, M. AU - Gottschlich, A.* AU - Klaus, R.* AU - Marr, C. AU - von Bergwelt-Baildon, M.* AU - Rothenfusser, S.* AU - Levesque, M.P.* AU - Heppt, M.V.* AU - Endres, S. AU - Klein, C.* AU - Kobold, S. C1 - 67915 C2 - 54393 CY - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England TI - Bispecific antibodies redirect synthetic agonistic receptor modified T cells against melanoma. JO - J. Immunother. Cancer VL - 11 IS - 5 PB - Bmj Publishing Group PY - 2023 SN - 2051-1426 ER - TY - JOUR AU - Gottschlich, A.* AU - Thomas, M. AU - Gruenmeier, R.* AU - Lesch, S.* AU - Rohrbacher, L.* AU - Igl, V.* AU - Briukhovetska, D.* AU - Benmebarek, M.* AU - Dede, S.* AU - Mueller, K.* AU - Xu, T.* AU - Dhoqina, D.* AU - Umut, Ö.* AU - Maerkl, F.* AU - Robinson, S.* AU - Sendelhofert, A.* AU - Schulz, H.* AU - Vick, B. AU - Cadilha, B.L.* AU - Brabenec, R.* AU - Roeder, N.* AU - Rataj, F.* AU - Nueesch, M.* AU - Wellbrock, J.* AU - Modemann, F.* AU - Fiedler, W.* AU - Kellner, C.* AU - Herold, T.* AU - Paquet, D.* AU - Jeremias, I. AU - von Baumgarten, L.* AU - Endres, S. AU - Subklewe, M.* AU - Marr, C. AU - Kobold, S. C1 - 66969 C2 - 53466 SP - A31-A31 TI - Single-cell transcriptomic atlas-guided development of chimeric antigen-receptor (CAR) T cells for the treatment of acute myeloid leukemia. JO - J. Immunother. Cancer VL - 10 PY - 2022 SN - 2051-1426 ER - TY - JOUR AB - An innovative strategy for cancer therapy is to combine the inhibition of cancer cell-intrinsic oncogenic signaling with cancer cell-extrinsic immunological activation of the tumor microenvironment (TME). In general, such approaches will focus on two or more distinct molecular targets in the malignant cells and in cells of the surrounding TME. In contrast, the protease Mucosa-associated lymphoid tissue protein 1 (MALT1) represents a candidate to enable such a dual approach by engaging only a single target. Originally identified and now in clinical trials as a lymphoma drug target based on its role in the survival and proliferation of malignant lymphomas addicted to chronic B cell receptor signaling, MALT1 proteolytic activity has recently gained additional attention through reports describing its tumor-promoting roles in several types of non-hematological solid cancer, such as breast cancer and glioblastoma. Besides cancer cells, regulatory T (Treg) cells in the TME are particularly dependent on MALT1 to sustain their immune-suppressive functions, and MALT1 inhibition can selectively reprogram tumor-infiltrating Treg cells into Foxp3-expressing proinflammatory antitumor effector cells. Thereby, MALT1 inhibition induces local inflammation in the TME and synergizes with anti-PD-1 checkpoint blockade to induce antitumor immunity and facilitate tumor control or rejection. This new concept of boosting tumor immunotherapy in solid cancer by MALT1 precision targeting in the TME has now entered clinical evaluation. The dual effects of MALT1 inhibitors on cancer cells and immune cells therefore offer a unique opportunity for combining precision oncology and immunotherapy to simultaneously impair cancer cell growth and neutralize immunosuppression in the TME. Further, MALT1 targeting may provide a proof of concept that modulation of Treg cell function in the TME represents a feasible strategy to augment the efficacy of cancer immunotherapy. Here, we review the role of MALT1 protease in physiological and oncogenic signaling, summarize the landscape of tumor indications for which MALT1 is emerging as a therapeutic target, and consider strategies to increase the chances for safe and successful use of MALT1 inhibitors in cancer therapy. AU - Mempel, T.R.* AU - Krappmann, D. C1 - 66468 C2 - 52830 TI - Combining precision oncology and immunotherapy by targeting the MALT1 protease. JO - J. Immunother. Cancer VL - 10 IS - 10 PY - 2022 SN - 2051-1426 ER - TY - JOUR AB - BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has proven its clinical utility in hematological malignancies. Optimization is still required for its application in solid tumors. Here, the lack of cancer-specific structures along with tumor heterogeneity represent a critical barrier to safety and efficacy. Modular CAR T cells indirectly binding the tumor antigen through CAR-adaptor molecules have the potential to reduce adverse events and to overcome antigen heterogeneity. We hypothesized that a platform utilizing unique traits of clinical grade antibodies for selective CAR targeting would come with significant advantages. Thus, we developed a P329G-directed CAR targeting the P329G mutation in the Fc part of tumor-targeting human antibodies containing P329G L234A/L235A (LALA) mutations for Fc silencing. METHODS: A single chain variable fragment-based second generation P329G-targeting CAR was retrovirally transduced into primary human T cells. These CAR T cells were combined with IgG1 antibodies carrying P329G LALA mutations in their Fc part targeting epidermal growth factor receptor (EGFR), mesothelin (MSLN) or HER2/neu. Mesothelioma, pancreatic and breast cancer cell lines expressing the respective antigens were used as target cell lines. Efficacy was evaluated in vitro and in vivo in xenograft mouse models. RESULTS: Unlike CD16-CAR T cells, which bind human IgG in a non-selective manner, P329G-targeting CAR T cells revealed specific effector functions only when combined with antibodies carrying P329G LALA mutations in their Fc part. P329G-targeting CAR T cells cannot be activated by an excess of human IgG. P329G-directed CAR T cells combined with a MSLN-targeting P329G-mutated antibody mediated pronounced in vitro and in vivo antitumor efficacy in mesothelioma and pancreatic cancer models. Combined with a HER2-targeting antibody, P329G-targeting CAR T cells showed substantial in vitro activation, proliferation, cytokine production and cytotoxicity against HER2-expressing breast cancer cell lines and induced complete tumor eradication in a breast cancer xenograft mouse model. The ability of the platform to target multiple antigens sequentially was shown in vitro and in vivo. CONCLUSIONS: P329G-targeting CAR T cells combined with antigen-binding human IgG1 antibodies containing the P329G Fc mutation mediate pronounced in vitro and in vivo effector functions in different solid tumor models, warranting further clinical translation of this concept. AU - Stock, S.* AU - Benmebarek, M.R.* AU - Kluever, A.K.* AU - Darowski, D.* AU - Jöst, C.* AU - Stubenrauch, K.G.* AU - Benz, J.* AU - Freimoser-Grundschober, A.* AU - Moessner, E.* AU - Umaña, P.* AU - Subklewe, M.* AU - Endres, S. AU - Klein, C.* AU - Kobold, S. C1 - 65850 C2 - 52941 TI - Chimeric antigen receptor T cells engineered to recognize the P329G-mutated Fc part of effector-silenced tumor antigen-targeting human IgG1 antibodies enable modular targeting of solid tumors. JO - J. Immunother. Cancer VL - 10 IS - 7 PY - 2022 SN - 2051-1426 ER - TY - JOUR AB - Background Although antibodies blocking immune checkpoints have already been approved for clinical cancer treatment, the mechanisms involved are not yet completely elucidated. Here we used a λ-MYC transgenic model of endogenously growing B-cell lymphoma to analyze the requirements for effective therapy with immune checkpoint inhibitors. Methods Growth of spontaneous lymphoma was monitored in mice that received antibodies targeting programmed cell death protein 1 and cytotoxic T lymphocyte-associated protein-4, and the role of different immune cell compartments and cytokines was studied by in vivo depletion experiments. Activation of T and natural killer cells and the induction of tumor senescence were analyzed by flow cytometry. Results On immune checkpoint blockade, visible lymphomas developed at later time points than in untreated controls, indicating an enhanced tumor control. Importantly, 20% to 30% of mice were even long-term protected and did never develop clinical signs of tumor growth. The therapeutic effect was dependent on cytokine-induced senescence in malignant B cells. The proinflammatory cytokines interferon-γ(IFN- 3) and tumor necrosis factor (TNF) were necessary for the survival benefit as well as for senescence induction in the λ-MYC model. Antibody therapy improved T-cell functions such as cytokine production, and long-time survivors were only observed in the presence of T cells. Yet, NK cells also had a pronounced effect on therapy-induced delay of tumor growth. Antibody treatment enhanced numbers, proliferation and IFN-γexpression of NK cells in developing tumors. The therapeutic effect was fully abrogated only after depletion of both, T cells and NK cells, or after ablation of either IFN-γor TNF. Conclusions Tumor cell senescence may explain why patients responding to immune checkpoint blockade frequently show stable growth arrest of tumors rather than complete tumor regression. In the lymphoma model studied, successful therapy required both, tumor-directed T-cell responses and NK cells, which control, at least partly, tumor development through cytokine-induced tumor senescence. AU - Ahmetlic, F. AU - Fauser, J. AU - Riedel, T. AU - Bauer, V. AU - Flessner, C. AU - Hömberg, N. AU - Hennel, R.* AU - Brenner, E.* AU - Lauber, K.* AU - Röcken, M.* AU - Mocikat, R. C1 - 61018 C2 - 50008 CY - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England TI - Therapy of lymphoma by immune checkpoint inhibitors: The role of T cells, NK cells and cytokine-induced tumor senescence. JO - J. Immunother. Cancer VL - 9 IS - 1 PB - Bmj Publishing Group PY - 2021 SN - 2051-1426 ER - TY - JOUR AU - Keller, P.* AU - Mazo, I.* AU - Gao, Y.* AU - Reddy, V.* AU - Caballero, F.* AU - Kazer, S.* AU - Fu, A.* AU - Sun, Y.* AU - Miller, D.* AU - Gianani, R.* AU - Marvin, J.* AU - Stephens, B.* AU - Beatty, G.* AU - Jenkins, R.* AU - von Andrian, U.* AU - Krappmann, D. AU - Mempel, T.* C1 - 64768 C2 - 51974 SP - A902-A902 TI - Reprogramming regulatory T cells (TREG) using a MALT1 inhibitor for cancer therapy. JO - J. Immunother. Cancer VL - 9 PY - 2021 SN - 2051-1426 ER - TY - JOUR AB - Background Acute myeloid leukemia (AML) is a hematopoietic malignancy which is biologically, phenotypically and genetically very heterogeneous. Outcome of patients with AML remains dismal, highlighting the need for improved, less toxic therapies. Chimeric antigen receptor T-cell (CART) immunotherapies for patients with refractory or relapse (R/R) AML are challenging because of the absence of a universal pan-AML target antigen and the shared expression of target antigens with normal hematopoietic stem/progenitor cells (HSPCs), which may lead to life-threating on-target/off-tumor cytotoxicity. CD33-redirected and CD123-redirected CARTs for AML are in advanced preclinical and clinical development, and they exhibit robust antileukemic activity. However, preclinical and clinical controversy exists on whether such CARTs are myeloablative. Methods We set out to comparatively characterize in vitro and in vivo the efficacy and safety of 41BB-based and CD28-based CARCD123. We analyzed 97 diagnostic and relapse AML primary samples to investigate whether CD123 is a suitable immunotherapeutic target, and we used several xenograft models and in vitro assays to assess the myeloablative potential of our second-generation CD123 CARTs. Results Here, we show that CD123 represents a bona fide target for AML and show that both 41BB-based and CD28-based CD123 CARTs are very efficient in eliminating both AML cell lines and primary cells in vitro and in vivo. However, both 41BB-based and CD28-based CD123 CARTs ablate normal human hematopoiesis and prevent the establishment of de novo hematopoietic reconstitution by targeting both immature and myeloid HSPCs. Conclusions This study calls for caution when clinically implementing CD123 CARTs, encouraging its preferential use as a bridge to allo-HSCT in patients with R/R AML. AU - Baroni, M.L.* AU - Sanchez Martinez, D.* AU - Gutierrez Aguera, F.* AU - Roca Ho, H.* AU - Castella, M.* AU - Zanetti, S.* AU - Velasco Hernandez, T.* AU - Diaz de la Guardia, R.* AU - Castaño, J.* AU - Anguita, E.* AU - Vives, S.* AU - Nomdedeu, J.* AU - Lapillone, H.* AU - Bras, A.E.* AU - van der Velden, V.H.J.* AU - Junca, J.* AU - Marin, P.* AU - Bataller, A.* AU - Esteve, J.* AU - Vick, B. AU - Jeremias, I. AU - Lopez, A.* AU - Sorigue, M.* AU - Bueno, C.* AU - Menendez, P.* C1 - 59357 C2 - 48758 CY - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England TI - 41BB-based and CD28-based CD123-redirected T-cells ablate human normal hematopoiesis in vivo. JO - J. Immunother. Cancer VL - 8 IS - 1 PB - Bmj Publishing Group PY - 2020 SN - 2051-1426 ER - TY - JOUR AU - Bauer, V. AU - Ahmetlic, F. AU - Roecken, M.* AU - Mocikat, R. C1 - 60190 C2 - 49828 SP - A467-A468 TI - Immune checkpoint blockade impacts the suppressive phenotype and function of regulatory T cells in an endogenous mouse lymphoma model. JO - J. Immunother. Cancer VL - 8 PY - 2020 SN - 2051-1426 ER - TY - JOUR AB - The present review summarizes up-to-date evidence addressing the frequently discussed clinical controversies regarding the use of immune checkpoint inhibitors (ICIs) in cancer patients with viral infections, including AIDS, hepatitis B and C, progressive multifocal leukoencephalopathy, influenza, and COVID-19. In detail, we provide available information on (1) safety regarding the risk of new infections, (2) effects on the outcome of pre-existing infections, (3) whether immunosuppressive drugs used to treat ICI-related adverse events affect the risk of infection or virulence of pre-existing infections, (4) whether the use of vaccines in ICI-treated patients is considered safe, and (5) whether there are beneficial effects of ICIs that even qualify them as a therapeutic approach for these viral infections. AU - Gambichler, T.* AU - Reuther, J.* AU - Scheel, C. AU - Becker, J.C.* C1 - 59578 C2 - 48854 CY - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England TI - On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19. JO - J. Immunother. Cancer VL - 8 IS - 2 PB - Bmj Publishing Group PY - 2020 SN - 2051-1426 ER - TY - JOUR AU - Yanchun, M. AU - Bauer, V. AU - Riedel, T. AU - Hofer, T.P. AU - Roecken, M.* AU - Mocikat, R. C1 - 60189 C2 - 49827 SP - A500 TI - Interleukin-10 drives the development of T regulatory type 1 (Tr1) cells and is a target for immunotherapy. JO - J. Immunother. Cancer VL - 8 PY - 2020 SN - 2051-1426 ER - TY - JOUR AB - Background: Tumor progression is accompanied by dramatic remodeling of the surrounding extracellular matrix leading to the formation of a tumor-specific ECM, which is often more collagen-rich and of increased stiffness. The altered ECM of the tumor supports cancer growth and metastasis, but it is unknown if this effect involves modulation of T cell activity. To investigate if a high-density tumor-specific ECM could influence the ability of T cells to kill cancer cells, we here studied how T cells respond to 3D culture in different collagen densities.Methods: T cells cultured in 3D conditions surrounded by a high or low collagen density were imaged using confocal fluorescent microscopy. The effects of the different collagen densities on T cell proliferation, survival, and differentiation were examined using flow cytometry. Cancer cell proliferation in similar 3D conditions was also measured. Triple-negative breast cancer specimens were analyzed for the number of infiltrating CD8+ T cells and for the collagen density. Whole-transcriptome analyses were applied to investigate in detail the effects of collagen density on T cells. Computational analyses were used to identify transcription factors involved in the collagen density-induced gene regulation. Observed changes were confirmed by qRT-PCR analysis.Results: T cell proliferation was significantly reduced in a high-density matrix compared to a low-density matrix and prolonged culture in a high-density matrix led to a higher ratio of CD4+ to CD8+ T cells. The proliferation of cancer cells was unaffected by the surrounding collagen-density. Consistently, we observed a reduction in the number of infiltrating CD8+ T-cells in mammary tumors with high collagen-density indicating that collagen-density has a role in regulating T cell abundance in human breast cancer.Whole-transcriptome analysis of 3D-cultured T cells revealed that a high-density matrix induces downregulation of cytotoxic activity markers and upregulation of regulatory T cell markers. These transcriptional changes were predicted to involve autocrine TGF-beta signaling and they were accompanied by an impaired ability of tumor-infiltrating T cells to kill autologous cancer cells.Conclusions: Our study identifies a new immune modulatory mechanism, which could be essential for suppression of T cell activity in the tumor microenvironment. AU - Kuczek, D.E.* AU - Larsen, A.M.H.* AU - Thorseth, M.L.* AU - Carretta, M.* AU - Kalvisa, A.* AU - Siersbæk, M.S.* AU - Simões, A.M.C.* AU - Roslind, A.* AU - Engelholm, L.H.* AU - Nößner, E. AU - Donia, M.* AU - Svane, I.M.* AU - Straten, P.T.* AU - Grøntved, L.* AU - Madsen, D.H.* C1 - 55686 C2 - 46519 CY - Campus, 4 Crinan St, London N1 9xw, England TI - Collagen density regulates the activity of tumor-infiltrating T cells. JO - J. Immunother. Cancer VL - 7 IS - 1 PB - Bmc PY - 2019 SN - 2051-1426 ER -