Predictors of responses to immune checkpoint blockade in advanced melanoma
Open Access
- 19 September 2017
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 8 (1), 1-13
- https://doi.org/10.1038/s41467-017-00608-2
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.Keywords
This publication has 70 references indexed in Scilit:
- Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced CancerThe New England Journal of Medicine, 2012
- Colocalization of Inflammatory Response with B7-H1 Expression in Human Melanocytic Lesions Supports an Adaptive Resistance Mechanism of Immune EscapeScience Translational Medicine, 2012
- A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanomaJournal of Translational Medicine, 2011
- Clinical Experiences With Anti-CD137 and Anti-PD1 Therapeutic AntibodiesSeminars in Oncology, 2010
- Improved Endpoints for Cancer Immunotherapy TrialsJNCI Journal of the National Cancer Institute, 2010
- Sipuleucel-T Immunotherapy for Castration-Resistant Prostate CancerThe New England Journal of Medicine, 2010
- Single‐institution experience with ipilimumab in advanced melanoma patients in the compassionate use settingCancer, 2010
- Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response CriteriaClinical Cancer Research, 2009
- Circulating apoptotic proteins are increased in long-term disease-free breast cancer survivorsActa Oncologica, 2006
- Phase 1/2 study of subcutaneous and intradermal immunization with a recombinant MAGE-3 protein in patients with detectable metastatic melanomaInternational Journal of Cancer, 2005