Tumor-Intrinsic Sirpa Promotes Sensitivity to Checkpoint Inhibition Immunotherapy in Melanoma

Authors

Zhicheng Zhou
Mei-Ju May Chen
Yikai Luo
Kamalika Mojumdar
Xin Peng
Hu Chen
Shweta V Kumar
Rehan Akbani
Yiling Lu
Han Liang

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

Comments

Supplementary Material

PMID: 36332624

DOI

10.1016/j.ccell.2022.10.012

PMID

36332624

PMCID

PMC9669221

PubMedCentral® Posted Date

November 2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes