Canale, Fernando P; Neumann, Julia; von Renesse, Janusz; Loggi, Elisabetta; Pecoraro, Matteo; Vogel, Ian; Zoppi, Giada; Antonini, Gaia; Wolf, Tobias; Jin, Wenjie; Zheng, Xiaoqin; La Barba, Giuliano; Birgin, Emrullah; Forkel, Marianne; Nilsson, Tobias; Marone, Romina; Mueller, Henrik; Pelletier, Nadege; Jeker, Lukas T; Civenni, Gianluca; ... (2023). Proteomics of immune cells from liver tumors reveals immunotherapy targets. Cell genomics, 3(6), p. 100331. Elsevier 10.1016/j.xgen.2023.100331
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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 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 immune cell proteomes in liver cancer.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology |
UniBE Contributor: |
Schlapbach, Christoph |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2666-979X |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
03 Jul 2023 09:52 |
Last Modified: |
16 Jul 2023 02:26 |
Publisher DOI: |
10.1016/j.xgen.2023.100331 |
PubMed ID: |
37388918 |
Uncontrolled Keywords: |
CRISPR in mouse T cells HCC NK cells T cells cancer immunotherapy liver cancer macrophages mass spectrometry-based proteomics profiles of tumor-infiltrating immune cells proteomes |
BORIS DOI: |
10.48350/184294 |
URI: |
https://boris.unibe.ch/id/eprint/184294 |
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