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.

Proteomics of immune cells from liver tumors reveals immunotherapy targets / 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; Schlapbach, Christoph; Catapano, Carlo V; Seifert, Lena; Seifert, Adrian M; Gillessen, Silke; De Dosso, Sara; Cristaudi, Alessandra; Rahbari, Nuh N; Ercolani, Giorgio; Geiger, Roger. - In: CELL GENOMICS. - ISSN 2666-979X. - ELETTRONICO. - 3:6(2023), pp. 100331.1-100331.25. [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.
2023
Proteomics of immune cells from liver tumors reveals immunotherapy targets / 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; Schlapbach, Christoph; Catapano, Carlo V; Seifert, Lena; Seifert, Adrian M; Gillessen, Silke; De Dosso, Sara; Cristaudi, Alessandra; Rahbari, Nuh N; Ercolani, Giorgio; Geiger, Roger. - In: CELL GENOMICS. - ISSN 2666-979X. - ELETTRONICO. - 3:6(2023), pp. 100331.1-100331.25. [10.1016/j.xgen.2023.100331]
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; Schlapbach, Christoph; Catapano, Carlo V; Seifert, Lena; Seifert, Adrian M; Gillessen, Silke; De Dosso, Sara; Cristaudi, Alessandra; Rahbari, Nuh N; Ercolani, Giorgio; Geiger, Roger
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/961474
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