Proteomics of immune cells from liver tumors reveals immunotherapy targets.

ABSTRACT: Elucidating the mechanisms by which immune cells become dysfunctional in tumors is critical to developing next-generation immunotherapies. We profiled proteomes of cancer tissue as well as monocyte/macrophages, CD4⁺ and CD8⁺ T cells, and NK cells isolated from tumors, liver, and blood of 48 patients with hepatocellular carcinoma. We found that tumor macrophages induce the sphingosine-1-phospate-degrading enzyme SGPL1, which dampened their inflammatory phenotype and anti-tumor function in vivo. We further discovered that the signaling scaffold protein AFAP1L2, typically only found in activated NK cells, is also upregulated in chronically stimulated CD8⁺ T cells in tumors. Ablation of AFAP1L2 in CD8⁺ T cells increased their viability

SUBMITTER: Canale FP 

PROVIDER: S-EPMC10300607 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature