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Kaesler, S.* ; Wölbing, F.* ; Kempf, W.E.* ; Skabytska, Y. ; Köberle, M.* ; Volz, T.* ; Sinnberg, T.* ; Amaral, T.* ; Möckel, S.* ; Yazdi, A.* ; Metzler, G.* ; Schaller, M.* ; Hartmann, K.* ; Weide, B.* ; Garbe, C.* ; Rammensee, H.G.* ; Röcken, M.* ; Biedermann, T.

Targeting tumor-resident mast cells for effective anti-melanoma immune responses.

JCI insight 4:e125057 (2019)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Immune checkpoint blockade has revolutionized cancer treatment, Patients developing immune mediated adverse events, such as colitis, appear to particularly benefit from immune checkpoint inhibition. Yet, the contributing mechanisms are largely unknown. We identified a systemic LP5 signature in melanoma patients with colitis following anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) checkpoint inhibitor treatment and hypothesized that intestinal microbiota-derived LPS contributes to therapeutic efficacy. Because activation of immune cells within the tumor microenvironment is considered most promising to effectively control cancer, we analyzed human and murine melanoma for known sentinels of LPS. We identified mast cells (MCs) accumulating in and around melanomas and showed that effective melanoma immune control was dependent on LP5-activated MCs recruiting tumor-infiltrating effector T cells by secretion of CXCL10. Importantly, CXCL10 was also upregulated in human melanomas with immune regression and in patients with colitis induced by anti-CTLA-4 antibody. Furthermore, we demonstrate that CXCL10 upregulation and an MC signature at the site of melanomas are biomarkers for better patient survival, These findings provide conclusive evidence for a "Trojan horse treatment strategy" in which the plasticity of cancer-resident immune cells, such as MCs, is used as a target to boost tumor immune defense.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Chemokines ; Immunology ; Mast Cells ; Melanoma ; Oncology; Spontaneous Regression; Combined Nivolumab; Cancer; Blockade; Innate; Immunotherapy; Therapy; Microbiota; Inhibition; Ipilimumab
Sprache englisch
Veröffentlichungsjahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 2379-3708
e-ISSN 2379-3708
Zeitschrift JCI insight
Quellenangaben Band: 4, Heft: 19, Seiten: , Artikelnummer: e125057 Supplement: ,
Verlag Clarivate
Verlagsort Ann Arbor, Michigan
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Allergy Research (IAF)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Allergy
PSP-Element(e) G-522200-001
DOI 10.1172/jci.insight.125057
WOS ID WOS:000488988500001
Scopus ID 85072984168
PubMed ID 31578309
Erfassungsdatum 2019-10-07
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