TMEM123 a key player in immune surveillance of colorectal cancer
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 an...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1194087/full |
| _version_ | 1827891137739751424 |
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| author | Elisa Pesce Chiara Cordiglieri Mauro Bombaci Serenella Eppenberger-Castori Stefania Oliveto Cristina Manara Mariacristina Crosti Caner Ercan Mairene Coto Andrea Gobbini Susanna Campagnoli Tiziano Donnarumma Manuele Martinelli Valeria Bevilacqua Elisa De Camilli Paola Gruarin Maria L. Sarnicola Elisa Cassinotti Ludovica Baldari Giuseppe Viale Giuseppe Viale Stefano Biffo Stefano Biffo Sergio Abrignani Sergio Abrignani Luigi M. Terracciano Luigi M. Terracciano Renata Grifantini Renata Grifantini |
| author_facet | Elisa Pesce Chiara Cordiglieri Mauro Bombaci Serenella Eppenberger-Castori Stefania Oliveto Cristina Manara Mariacristina Crosti Caner Ercan Mairene Coto Andrea Gobbini Susanna Campagnoli Tiziano Donnarumma Manuele Martinelli Valeria Bevilacqua Elisa De Camilli Paola Gruarin Maria L. Sarnicola Elisa Cassinotti Ludovica Baldari Giuseppe Viale Giuseppe Viale Stefano Biffo Stefano Biffo Sergio Abrignani Sergio Abrignani Luigi M. Terracciano Luigi M. Terracciano Renata Grifantini Renata Grifantini |
| author_sort | Elisa Pesce |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T21:20:34Z |
| format | Article |
| id | doaj.art-2866ad7ef84346fea2d934d5f15aa946 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T21:20:34Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2866ad7ef84346fea2d934d5f15aa9462023-07-28T19:19:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11940871194087TMEM123 a key player in immune surveillance of colorectal cancerElisa Pesce0Chiara Cordiglieri1Mauro Bombaci2Serenella Eppenberger-Castori3Stefania Oliveto4Cristina Manara5Mariacristina Crosti6Caner Ercan7Mairene Coto8Andrea Gobbini9Susanna Campagnoli10Tiziano Donnarumma11Manuele Martinelli12Valeria Bevilacqua13Elisa De Camilli14Paola Gruarin15Maria L. Sarnicola16Elisa Cassinotti17Ludovica Baldari18Giuseppe Viale19Giuseppe Viale20Stefano Biffo21Stefano Biffo22Sergio Abrignani23Sergio Abrignani24Luigi M. Terracciano25Luigi M. Terracciano26Renata Grifantini27Renata Grifantini28Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, ItalyIstituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, ItalyIstituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, ItalyInstitute of Pathology, University Hospital Basel, Basel, SwitzerlandIstituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, ItalyIstituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, ItalyIstituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, ItalyInstitute of Pathology, University Hospital Basel, Basel, SwitzerlandInstitute of Pathology, University Hospital Basel, Basel, SwitzerlandIstituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, ItalyCheckmAb Srl, Milan, ItalyCheckmAb Srl, Milan, ItalyCheckmAb Srl, Milan, ItalyIstituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Pathology, European Institute of Oncology, Milan, ItalyIstituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, ItalyIstituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Surgery, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Surgery, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Pathology, European Institute of Oncology, Milan, ItalyDepartment of Oncology and Hemato-oncology, Università degli Studi di Milano, Milan, ItalyIstituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Biosciences, Università degli Studi di Milano, Milan, ItalyIstituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, ItalyIRCCS Humanitas Research Hospital, Rozzano, Italy0Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, ItalyIstituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, ItalyCheckmAb Srl, Milan, ItalyColorectal 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1194087/fullcolorectal cancertumor microenvironmenttumor-infiltrating lymphocytesTMEM123cytoskeleton organizationcell adhesion |
| spellingShingle | Elisa Pesce Chiara Cordiglieri Mauro Bombaci Serenella Eppenberger-Castori Stefania Oliveto Cristina Manara Mariacristina Crosti Caner Ercan Mairene Coto Andrea Gobbini Susanna Campagnoli Tiziano Donnarumma Manuele Martinelli Valeria Bevilacqua Elisa De Camilli Paola Gruarin Maria L. Sarnicola Elisa Cassinotti Ludovica Baldari Giuseppe Viale Giuseppe Viale Stefano Biffo Stefano Biffo Sergio Abrignani Sergio Abrignani Luigi M. Terracciano Luigi M. Terracciano Renata Grifantini Renata Grifantini TMEM123 a key player in immune surveillance of colorectal cancer Frontiers in Immunology colorectal cancer tumor microenvironment tumor-infiltrating lymphocytes TMEM123 cytoskeleton organization cell adhesion |
| title | TMEM123 a key player in immune surveillance of colorectal cancer |
| title_full | TMEM123 a key player in immune surveillance of colorectal cancer |
| title_fullStr | TMEM123 a key player in immune surveillance of colorectal cancer |
| title_full_unstemmed | TMEM123 a key player in immune surveillance of colorectal cancer |
| title_short | TMEM123 a key player in immune surveillance of colorectal cancer |
| title_sort | tmem123 a key player in immune surveillance of colorectal cancer |
| topic | colorectal cancer tumor microenvironment tumor-infiltrating lymphocytes TMEM123 cytoskeleton organization cell adhesion |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1194087/full |
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