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TMEM123 a key player in immune surveillance of colorectal cancer.

ABSTRACT: 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.

SUBMITTER: Pesce E

PROVIDER: S-EPMC10327427 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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TMEM123 a key player in immune surveillance of colorectal cancer.

Pesce Elisa E Cordiglieri Chiara C Bombaci Mauro M Eppenberger-Castori Serenella S Oliveto Stefania S Manara Cristina C Crosti Mariacristina M Ercan Caner C Coto Mairene M Gobbini Andrea A Campagnoli Susanna S Donnarumma Tiziano T Martinelli Manuele M Bevilacqua Valeria V De Camilli Elisa E Gruarin Paola P Sarnicola Maria L ML Cassinotti Elisa E Baldari Ludovica L Viale Giuseppe G Biffo Stefano S Abrignani Sergio S Terracciano Luigi M LM Grifantini Renata R

Frontiers in immunology 20230623

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 ...[more]

PMID: 37426665

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Project description:This study investigates immune priming effects associated with granulocytes in crickets through a comprehensive analysis. Kaplan-Meier survival analysis reveals a significant contrast in survival rates, with the heat-killed Bacillus thuringiensis (Bt)-primed group (B-1) exhibiting an impressive ~80% survival rate compared to the PBS buffer-primed group (A-1) with only ~10% survival 60 hours post live Bt infection. Hemocyte analysis underscores elevated hemocyte counts, particularly in granulocytes of the B-1 group, suggesting a correlation between heat-killed Bt priming and heightened immune activation. Microscopy techniques further explore granulocyte morphology, unveiling distinctive immune responses in the B-1 group characterized by prolonged immune activation, heightened granulocyte activity, phagocytosis, and extracellular trap formation, contributing to enhanced survival rates. In particular, after 24 hours of injecting live Bt, most granulocytes in the A-1 group exhibited ETosis (death with release of extracellular traps), while in the B-1 group, the majority of granulocytes were observed to maintain highly activated extracellular traps, sustaining the immune response. Gene expression analysis supports these findings, revealing differential regulation of immune-related genes such as antibacterial humoral response, detection of bacterial lipopeptides, and cellular response to bacteria lipopeptides. Additionally, groups A (preinjected with heat-killed Bt), B (preinjected with heat-killed E. coli), and C (preinjected with PBS) were re- injected with live Bt and evaluated for survival rates over two- and nine-day intervals. Two days later, only group C displayed low survival rates. After injecting live Bt 9 days later, group B surprisingly showed a similarly low survival rate, while group A exhibited a high survival rate of ~60% after 60 hours, with actively moving and healthy crickets. In conclusion, this research provides valuable insights into both short-term and long-term immune priming effects in crickets, contributing to our understanding of invertebrate immunity with potential applications in public health.

Dataset Information

TMEM123 a key player in immune surveillance of colorectal cancer.

Publications

TMEM123 a key player in immune surveillance of colorectal cancer.

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