Immune and molecular correlates in melanoma treated with immune checkpoint blockade
2017
Immunotherapy for metastatic
melanomahas a decades-long history, and the relatively recent use of checkpoint inhibitors has revolutionized treatment. Durable and sometimes complete remission of metastatic
melanomais now achievable in some patients who receive checkpoint-blocking therapy. However, it is unclear why some patients fare better than others. This review highlights several molecular indicators of response to checkpoint inhibition in metastatic
melanoma, focusing on tumor programmed death ligand 1 expression, major histocompatibility
complex classI expression, mutational load in the tumor, and T-cell infiltration into the tumor. In addition, clinical correlates of response, notably
vitiligoand other immune-related adverse events, can potentially shed light on the mechanisms by which checkpoint blockade may achieve such great success, particularly in
melanoma. The authors propose that
microphthalmia-associated transcription factor—a key regulator of
melanocytesurvival, melanin production, and
melanomatransformation—produces a molecular landscape in
melanocytesand
melanomacells that can make
melanomasparticularly susceptible to checkpoint blockade and also can result in immune attack on normal
melanocytes. Cancer 2017;123:2143-53. © 2017 American Cancer Society.
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