Dataset Information

Predictors of responses to immune checkpoint blockade in advanced melanoma.

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.

SUBMITTER: Jacquelot N

PROVIDER: S-EPMC5605517 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Predictors of responses to immune checkpoint blockade in advanced melanoma.

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

Nature communications 20170919 1

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 immun ...[more]

PMID: 28928380

Similar Datasets

Project description:ImportanceImmune checkpoint blockade (ICB) has improved the survival of patients with advanced melanoma. Durable responses are observed for 40% to 60% of patients, depending on treatment regimens. However, there is still large variability in the response to treatment with ICB, and patients experience a range of immune-related adverse events of differing severity. Nutrition, through its association with the immune system and gut microbiome, is a poorly explored but appealing target with potential to improve the efficacy and tolerability of ICB.ObjectiveTo investigate the association between habitual diet and response to treatment with ICB.Design, setting, and participantsThis multicenter cohort study (the PRIMM study) was conducted in cancer centers in the Netherlands and UK and included 91 ICB-naive patients with advanced melanoma who were receiving ICB between 2018 and 2021.ExposuresPatients were treated with anti-programmed cell death 1 and anti-cytotoxic T lymphocyte-associated antigen 4 monotherapy or combination therapy. Dietary intake was assessed through food frequency questionnaires before treatment.Main outcomes and measuresClinical end points were defined as overall response rate (ORR), progression-free survival at 12 months (PFS-12), and immune-related adverse events that were grade 2 or higher.ResultsThere were a total of 44 Dutch participants (mean [SD] age, 59.43 [12.74] years; 22 women [50%]) and 47 British participants (mean [SD] age, 66.21 [16.63] years; 15 women [32%]). Dietary and clinical data were prospectively collected from 91 patients receiving ICB between 2018 and 2021 for advanced melanoma in the UK and the Netherlands. Logistic generalized additive models revealed positive linear associations between a Mediterranean dietary pattern that was high in whole grains, fish, nuts, fruit, and vegetables and the probability of ORR and PFS-12 (probability of 0.77 for ORR; P = .02; false discovery rate, 0.032; effective degrees of freedom, 0.83; probability of 0.74 for PFS-12; P = .01; false discovery rate, 0.021; effective degrees of freedom, 1.54).Conclusions and relevanceThis cohort study found a positive association between a Mediterranean diet, a widely recommended model of healthy eating, and response to treatment with ICB. Large prospective studies from different geographies are needed to confirm the findings and further elucidate the role of diet in the context of ICB.

Dataset Information

Predictors of responses to immune checkpoint blockade in advanced melanoma.

Publications

Predictors of responses to immune checkpoint blockade in advanced melanoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets