Research ArticleCancer

Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses

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Science Translational Medicine  17 Feb 2021:
Vol. 13, Issue 581, eabd8636
DOI: 10.1126/scitranslmed.abd8636

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Spreading the immune response to melanoma

Immune checkpoint inhibitors (ICIs) have revolutionized treatment for patients with melanoma, although not all patients respond. Here, Lo et al. showed that patients with the best responses to ICI often develop immune responses to melanocyte-lineage epitopes. The authors then showed that inducing mutations in murine melanomas in combination with ICI resulted in T cell responses to the induced mutations plus inflammation that provoked epitope spreading to the targeting of healthy melanocyte antigens. The response to melanocyte antigens led to better long-term control of melanomas and rejection of secondary melanoma challenges a finding that was mimicked by alternatively inducing inflammation with localized laser and imiquimod treatment. Thus, combining methods to induce localized inflammation plus ICI may represent a therapeutic option for patients with suboptimal responses to ICI alone.

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