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 cells, 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 upon repeated stimulation and enhanced their antitumor activity synergistically with PD-L1 blockade in mouse models. Our data revealed new targets for immunotherapy and provide a resource on immune cell proteomes in liver cancer (www.immunomics.ch/liver).

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Monocyte, T Cell, Liver, Natural Killer Cell, Blood, Macrophage

SUBMITTER: Matteo Pecoraro  

LAB HEAD: Roger Geiger

PROVIDER: PXD040957 | Pride | 2023-04-19

REPOSITORIES: Pride