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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)
Publ. Version/Full Text Research data 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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Chemokines ; Immunology ; Mast Cells ; Melanoma ; Oncology; Spontaneous Regression; Combined Nivolumab; Cancer; Blockade; Innate; Immunotherapy; Therapy; Microbiota; Inhibition; Ipilimumab
ISSN (print) / ISBN 2379-3708
e-ISSN 2379-3708
Journal JCI insight
Quellenangaben Volume: 4, Issue: 19, Pages: , Article Number: e125057 Supplement: ,
Publisher Clarivate
Publishing Place Ann Arbor, Michigan
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Unit for Clinical Allergology (KKG-EKA)