RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Revealing the dynamics of follicular T cells and checkpoint engagement in surgically resected colorectal cancer and their relations to clinicopathological aspects.
Revealing the dynamics of follicular T cells and checkpoint engagement in surgically resected colorectal cancer and their relations to clinicopathological aspects.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
滤泡 T 细胞在 CRC 中富集且高度活化,尤其是在肿瘤微环境中。TIGIT + VISTA + 亚群占优势提示其在抗肿瘤免疫和免疫逃逸中具有双重作用。这些细胞可作为生物标志物和免疫治疗的潜在靶点。
滤泡T细胞参与B细胞反应和抗肿瘤免疫,但其免疫检查点表达及在结直肠癌(CRC)中的作用仍未被充分阐明。我们评估了CRC患者中滤泡辅助性和滤泡细胞毒性T细胞亚群(Tfh和Tfc)的分布、活化状态及检查点表达,以及它们与临床病理特征的相关性。
从埃及南部癌症研究所、艾斯尤特大学招募了33例CRC患者和25例健康对照。采用流式细胞术评估滤泡性T细胞亚群及其诱导性T细胞共刺激分子(ICOS)、含Ig和ITIM结构域的T细胞免疫受体(TIGIT)和V域Ig T细胞活化抑制因子(VISTA)的表达。
与对照组相比,CRC患者外周血中Tfh和Tfc细胞显著增加(分别为p < 0.001和p = 0.006)。其在TIL(肿瘤浸润淋巴细胞)(TILs)中的频率高于正常结肠组织(p = 0.002和p < 0.001)和外周血(p < 0.001)。与患者的正常组织和外周血相比,其ICOS表达在患者血液中显著升高(p = 0.008和p = 0.04),且在TIL中最高(p = 0.02)(p < 0.001)。TIGIT VISTA滤泡性T细胞亚群在患者外周血中显著扩增,在TILs中表达达到峰值(p < 0.001)。
Follicular T cells contribute to B-cell responses and antitumor immunity, yet their immune checkpoint expression and role in colorectal cancer (CRC) remain insufficiently characterized. We evaluated the distribution, activation status, and checkpoint expression of follicular helper and follicular cytotoxic T-cell subsets (Tfh and Tfc) in CRC patients and their association with clinicopathological features.
Thirty-three CRC patients and 25 healthy controls were recruited from South Egypt Cancer Institute, Assiut University. Flow cytometry was used to assess follicular T-cell subsets and their expression of inducible T-cell costimulatory (ICOS), T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and V-domain Ig Suppressor of T-cell Activation (VISTA).
Tfh and Tfc cells were significantly increased in peripheral blood of CRC patients compared with controls (p < 0.001 and p = 0.006, respectively). Their frequencies were higher in tumor-infiltrating lymphocytes (TILs) than in normal colonic tissue (p = 0.002 and p < 0.001) and peripheral blood (p < 0.001). Their ICOS expression was significantly elevated in patients' blood (p = 0.008 and p = 0.04) and highest in TIL (p = 0.02) compared to the normal tissue and peripheral blood of patients (p < 0.001). TIGIT VISTA follicular T-cell subsets were significantly expanded in the peripheral blood of patients, with peak expression in TILs (p < 0.001).
Follicular T cells are enriched and highly activated in CRC, particularly within the tumor microenvironment. The predominance of TIGIT + VISTA + subsets suggests a dual role in antitumor immunity and immune escape. These cells serve as biomarkers and potential targets for immunotherapy.
MEMBER ACCOUNT
登录成功会直接打开下一页。