Publication Date
11-14-2022
Journal
Cancer Cell
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
Keywords
Animals, Mice, B7-H1 Antigen, CD8-Positive T-Lymphocytes, Ecosystem, Immunotherapy, Melanoma, Proteomics, Humans
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Immunotherapy Commons, Medical Sciences Commons, Oncology Commons
Comments
Supplementary Materials
PMID: 36332624