Tumor-intrinsic SIRPA promotes sensitivity to checkpoint inhibition immunotherapy in melanoma.

ABSTRACT: Checkpoint inhibition immunotherapy has revolutionized cancer treatment, but many patients show resistance. Here we perform integrative transcriptomic and proteomic analyses on emerging immuno-oncology targets across multiple clinical cohorts of melanoma under anti-PD-1 treatment, on both bulk and single-cell levels. We reveal a surprising role of tumor-intrinsic SIRPA in enhancing antitumor immunity, in contrast to its well-established role as a major inhibitory immune modulator in macrophages. The loss of SIRPA expression is a marker of melanoma dedifferentiation, a key phenotype linked to immunotherapy efficacy. Inhibition of SIRPA in melanoma cells abrogates tumor killing by activated CD8⁺ T cells in a co-culture system. Mice bearing SIRPA-deficient melanoma tumors show no r

SUBMITTER: Zhou Z 

PROVIDER: S-EPMC9669221 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature