TMEM123 a key player in immune surveillance of colorectal cancer

Frontiers in Immunology

Immunology

Tiziano Donnarumma¹  Susanna Campagnoli¹  Manuele Martinelli¹  Elisa De Camilli²  Giuseppe Viale³  Elisa Cassinotti⁴  Ludovica Baldari⁴  Luigi M. Terracciano⁵  Caner Ercan⁶  Mairene Coto⁶  Serenella Eppenberger-Castori⁶  Andrea Gobbini⁷  Chiara Cordiglieri⁷  Maria L. Sarnicola⁷  Mauro Bombaci⁷  Stefania Oliveto⁷  Mariacristina Crosti⁷  Valeria Bevilacqua⁷  Cristina Manara⁷  Paola Gruarin⁷  Elisa Pesce⁷  Renata Grifantini⁸  Stefano Biffo⁹  Sergio Abrignani^1,10 

[1] CheckmAb Srl, Milan, Italy;Department of Pathology, European Institute of Oncology, Milan, Italy;Department of Pathology, European Institute of Oncology, Milan, Italy;Department of Oncology and Hemato-oncology, Università degli Studi di Milano, Milan, Italy;Department of Surgery, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy;IRCCS Humanitas Research Hospital, Rozzano, Italy;Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy;Institute of Pathology, University Hospital Basel, Basel, Switzerland;Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy;Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy;CheckmAb Srl, Milan, Italy;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;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;

关键词: colorectal cancer;    tumor microenvironment;    tumor-infiltrating lymphocytes;    TMEM123;    cytoskeleton organization;    cell adhesion;    migration;   

DOI  :  10.3389/fimmu.2023.1194087

 received in 2023-03-26, accepted in 2023-05-31,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
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