Istituto Nazionale Genetica Molecolare (INGM), Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
Institute of Pathology, University Hospital Basel, Basel, Switzerland.
Front Immunol. 2023 Jun 23;14:1194087. doi: 10.3389/fimmu.2023.1194087. eCollection 2023.
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.
结直肠癌（CRC）是癌症相关死亡的主要原因。在肿瘤部位，效应免疫细胞和癌细胞之间的相互作用决定了肿瘤消除或生长的平衡。我们发现，跨膜蛋白 123（TMEM123）在肿瘤浸润的 CD4 和 CD8 T 淋巴细胞中过度表达，并有助于其效应表型。浸润性 TMEM123+ CD8+ T 细胞的存在与更好的总生存期和无转移生存期相关。TMEM123 定位于浸润 T 细胞的突起中，有助于淋巴细胞迁移和细胞骨架组织。TMEM123 的沉默调节依赖于细胞骨架调节剂 WASP 和 Arp2/3 肌动蛋白成核复合物的基础信号通路，这对于突触力的发挥是必需的。使用肿瘤样细胞-淋巴细胞共培养实验，我们发现淋巴细胞通过 TMEM123 形成簇，锚定在癌细胞上，并有助于杀死癌细胞。我们提出 TMEM123 在肿瘤微环境中 T 细胞的抗癌活性中发挥积极作用。
