Predictors of responses to immune checkpoint blockade in advanced melanoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

N. Jacquelot, M. P. Roberti, D. P. Enot, S. Rusakiewicz, N. Ternès, S. Jegou, D. M. Woods, A. L. Sodré, M. Hansen, Y. Meirow, M. Sade-Feldman, A. Burra, S. S. Kwek, C. Flament, M. Messaoudene, C. P. M. Duong, L. Chen, B. S. Kwon, A. C. Anderson, V. K. Kuchroo, B. Weide, F. Aubin, C. Borg, S. Dalle, O. Beatrix, M. Ayyoub, B. Balme, G. Tomasic, A. M. Di Giacomo, M. Maio, D. Schadendorf, I. Melero, B. Dréno, A. Khammari, R. Dummer, M. Levesque, Y. Koguchi, L. Fong, M. Lotem, M. Baniyash, H. Schmidt, I. M. Svane, G. Kroemer, A. Marabelle, S. Michiels, A. Cavalcanti, M. J. Smyth, J. S. Weber, A. M. Eggermont, L. Zitvogel

ABSTRACT

Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8+ T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma. More... »

PAGES

592

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-017-00608-2

DOI

http://dx.doi.org/10.1038/s41467-017-00608-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1091688617

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28928380


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