Proteomics of immune cells from liver tumors reveals immunotherapy targets

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Fernando P Canale - , Institute for Research in Biomedicine (Author)
  • Julia Neumann - , Institute for Research in Biomedicine, Università della Svizzera italiana (Author)
  • Janusz von Renesse - , Department of Visceral, Thoracic and Vascular Surgery, National Center for Tumor Diseases (Partners: UKD, MFD, HZDR, DKFZ) (Author)
  • Elisabetta Loggi - , University of Bologna (Author)
  • Matteo Pecoraro - , Institute for Research in Biomedicine (Author)
  • Ian Vogel - , Institute for Research in Biomedicine (Author)
  • Giada Zoppi - , Institute for Research in Biomedicine (Author)
  • Gaia Antonini - , Institute for Research in Biomedicine (Author)
  • Tobias Wolf - , Institute for Research in Biomedicine (Author)
  • Wenjie Jin - , Institute for Research in Biomedicine (Author)
  • Xiaoqin Zheng - , Institute for Research in Biomedicine (Author)
  • Giuliano La Barba - , Morgagni-Pierantoni Hospital (Author)
  • Emrullah Birgin - , Heidelberg University  (Author)
  • Marianne Forkel - , F. Hoffmann-La Roche AG (Author)
  • Tobias Nilsson - , F. Hoffmann-La Roche AG (Author)
  • Romina Marone - , University of Basel (Author)
  • Henrik Mueller - , F. Hoffmann-La Roche AG (Author)
  • Nadege Pelletier - , F. Hoffmann-La Roche AG (Author)
  • Lukas T Jeker - , University of Basel (Author)
  • Gianluca Civenni - , Università della Svizzera italiana (Author)
  • Christoph Schlapbach - , University of Bern (Author)
  • Carlo V Catapano - , Università della Svizzera italiana (Author)
  • Lena Seifert - , Department of Visceral, Thoracic and Vascular Surgery, National Center for Tumor Diseases (Partners: UKD, MFD, HZDR, DKFZ) (Author)
  • Adrian M Seifert - , Department of Visceral, Thoracic and Vascular Surgery, National Center for Tumor Diseases (Partners: UKD, MFD, HZDR, DKFZ) (Author)
  • Silke Gillessen - , Università della Svizzera italiana (Author)
  • Sara De Dosso - , Università della Svizzera italiana (Author)
  • Alessandra Cristaudi - , Cantonal Hospital Lugano (Author)
  • Nuh N Rahbari - , Heidelberg University  (Author)
  • Giorgio Ercolani - , Department of Medical and Surgical Sciences - DIMEC (Author)
  • Roger Geiger - , Institute for Research in Biomedicine (Author)

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 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.

Details

Original languageEnglish
Article number100331
Pages (from-to)100331
JournalCell genomics
Volume3
Issue number6
Publication statusPublished - 14 Jun 2023
Peer-reviewedYes

External IDs

PubMedCentral PMC10300607
Scopus 85161832683
ORCID /0000-0002-5329-3164/work/147141087

Keywords

Sustainable Development Goals