Ann Pathol
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Costimulatory molecules allow the full lymphocyte activation, whereas co-inhibitory molecules are negative counterparts that act as immune regulators, avoiding excessive response. In some context of chronic inflammation such as cancer, co-inhibitory immune checkpoint as CTLA-4, PD-1, Lag-3, Tim-3 can accumulate at the membrane of T cells leading to a state of anergy and therefore the loss of tumor growth control. ⋯ Immunotherapy by anti-CTLA-4 and anti-PD-1/PD-L1 early demonstrated very good proof of efficacy in the setting of several cancers types, supporting the role of these molecules in tumor immune escape. The aim of this review is to summarize the pathophysiology of immune checkpoints and their therapeutic applications in cancer.
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Prognosis and treatment of advanced melanoma have been transformed by the success of immunotherapies, in particular agents targeting PD-1. PD-L1 expression assessed by immunohistochemistry in not an effective predictive biomarker to select patients in this tumor type, since significant clinical benefit was observed in the group of patients with negative tumors. ⋯ Other tissue biomarkers are emerging to identify sensitive tumors to anti-PD-1 agents. In particular, assessment of immune infiltrates in tumor tissue, mutational load and tumor neoantigens seem promising in melanoma.