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/macro-phages, CD4+ and CD8+ T cells, and NK cells isolated from tumors, liver, and blood of 48 patients with hepa-tocellular 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 up -regulated in chronically stimulated CD8+T cells in tumors. Ablation of AFAP1L2 in CD8+T cells increased their viability upon repeated stimulation and enhanced their anti-tumor activity synergistically with PD-L1 blockade in mouse models. Our data reveal new targets for immunotherapy and provide a resource on im-mune cell proteomes in liver cancer.
Canale, F.P., Neumann, J., von Renesse, J., Loggi, E., Pecoraro, M., Vogel, I., et al. (2023). Proteomics of immune cells from liver tumors reveals immunotherapy targets. CELL GENOMICS, 3(6), 1-25 [10.1016/j.xgen.2023.100331].
Proteomics of immune cells from liver tumors reveals immunotherapy targets
Loggi, Elisabetta;Ercolani, Giorgio;
2023
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/macro-phages, CD4+ and CD8+ T cells, and NK cells isolated from tumors, liver, and blood of 48 patients with hepa-tocellular 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 up -regulated in chronically stimulated CD8+T cells in tumors. Ablation of AFAP1L2 in CD8+T cells increased their viability upon repeated stimulation and enhanced their anti-tumor activity synergistically with PD-L1 blockade in mouse models. Our data reveal new targets for immunotherapy and provide a resource on im-mune cell proteomes in liver cancer.File | Dimensione | Formato | |
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2023-Canale (Genomics)-Proteomics of HCC.pdf
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