TMEM123 a key player in immune surveillance of colorectal cancer.

Autor:	Pesce E; Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Cordiglieri C; Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Bombaci M; Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Eppenberger-Castori S; Institute of Pathology, University Hospital Basel, Basel, Switzerland., Oliveto S; Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Manara C; Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Crosti M; Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Ercan C; Institute of Pathology, University Hospital Basel, Basel, Switzerland., Coto M; Institute of Pathology, University Hospital Basel, Basel, Switzerland., Gobbini A; Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Campagnoli S; CheckmAb Srl, Milan, Italy., Donnarumma T; CheckmAb Srl, Milan, Italy., Martinelli M; CheckmAb Srl, Milan, Italy., Bevilacqua V; Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., De Camilli E; Department of Pathology, European Institute of Oncology, Milan, Italy., Gruarin P; Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Sarnicola ML; Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy., Cassinotti E; Department of Surgery, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy., Baldari L; Department of Surgery, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy., Viale G; Department of Pathology, European Institute of Oncology, Milan, Italy.; Department of Oncology and Hemato-oncology, Università degli Studi di Milano, Milan, Italy., Biffo S; Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.; Department of Biosciences, Università degli Studi di Milano, Milan, Italy., Abrignani S; Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy., Terracciano LM; IRCCS Humanitas Research Hospital, Rozzano, Italy.; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy., Grifantini R; Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.; CheckmAb Srl, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Jun 23; Vol. 14, pp. 1194087. Date of Electronic Publication: 2023 Jun 23 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1194087
Abstrakt:	Colorectal cancer (CRC) is a leading cause of cancer-associated death. In the tumor site, the interplay between effector immune cells and cancer cells determines the balance between tumor elimination or outgrowth. We discovered that the protein TMEM123 is over-expressed in tumour-infiltrating CD4 and CD8 T lymphocytes and it contributes to their effector phenotype. The presence of infiltrating TMEM123+ CD8+ T cells is associated with better overall and metastasis-free survival. TMEM123 localizes in the protrusions of infiltrating T cells, it contributes to lymphocyte migration and cytoskeleton organization. TMEM123 silencing modulates the underlying signaling pathways dependent on the cytoskeletal regulator WASP and the Arp2/3 actin nucleation complex, which are required for synaptic force exertion. Using tumoroid-lymphocyte co-culture assays, we found that lymphocytes form clusters through TMEM123, anchoring to cancer cells and contributing to their killing. We propose an active role for TMEM123 in the anti-cancer activity of T cells within tumour microenvironment. Competing Interests: Author Renata Grifantini is currently employed by CheckmAb Srl. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Pesce, Cordiglieri, Bombaci, Eppenberger-Castori, Oliveto, Manara, Crosti, Ercan, Coto, Gobbini, Campagnoli, Donnarumma, Martinelli, Bevilacqua, De Camilli, Gruarin, Sarnicola, Cassinotti, Baldari, Viale, Biffo, Abrignani, Terracciano and Grifantini.)
Databáze:	MEDLINE
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