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:Differential expression of Tim3 protein in colorectal cancer associated with MSI and Braf mutation.
Differential expression of Tim3 protein in colorectal cancer associated with MSI and Braf mutation.
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Tim3是一种负性免疫检查点分子,在肿瘤诱导的免疫抑制中发挥关键作用。Tim3是一种细胞表面分子,表达于T细胞上,标志着多种癌症中功能失调的CD8+细胞。Tim3的表达主要在TIL(肿瘤浸润淋巴细胞)(TILs)中被报道。很少有研究关注Tim3在肿瘤细胞中的表达。采用免疫组化法测定Tim3表达水平。统计分析结直肠癌细胞和TIL(肿瘤浸润淋巴细胞)中Tim3表达与临床病理参数之间的关系。Tim3在TILs和结直肠癌细胞中的检测存在差异。结直肠癌细胞中Tim3阳性表达与肿瘤位置(P=0.001)、肿瘤浸润深度(P<0.001)、淋巴结转移(P=0.001)、TNM分期(P=0.001)、MSI(P=0.008)和Braf V600E突变(P=0.001)相关。
另一方面,TILs中Tim3阳性表达仅与肿瘤浸润深度相关(P<0.001)。结直肠癌细胞和TILs中Tim3阳性表达均与肿瘤浸润深度(P<0.001)、淋巴结转移(P=0.002)、TNM分期(P=0.002)、MSI(P=0.039)和Braf V600E突变(P=0.009)相关。Kaplan-Meier生存分析显示,结直肠癌和TILs中Tim3表达与患者总生存期(OS)率显著相关(P=0.039和0.001)。Tim3可能是结直肠癌的潜在预后标志物和治疗靶点。
Tim3 is a negative immune checkpoint molecule and plays a crucial part in tumor-induced immune suppression. Tim3 is a cell surface molecule expressed on T cells marking dysfunctional CD8+ cells in various kinds of cancers. Tim3 expression was mainly reported in tumor-infiltrating lymphocytes (TILs). There are few studies focusing on the expression of Tim3 in tumor cells. Immunohistochemistry was performed to determine Tim3 expression level. The relationships between Tim3 expression in colorectal cancer cells and in tumor-infiltrating lymphocytes and cilicopathological parameters were statistically analyzed. Tim3 was differentially detected in TILs and in colorectal cancer cells. Positive expression of Tim3 in colorectal cancer cells was associated with tumor location (P=0.
001), depth of tumor invasion (P<0. 001), lymph node metastasis (P=0. 001), TNM stage (P=0. 001), MSI (P=0. 008), and Braf V600E mutation (P=0. 001). On the other hand, positive expression of Tim3 in TILs was only related to depth of tumor invasion (P<0. 001). Positive expression of Tim3 in both colorectal cancer cells and TILs was associated with depth of tumor invasion (P<0.
001), lymph node metastasis (P=0. 002), TNM stage (P=0. 002), MSI (P=0. 039), and Braf V600E mutation (P=0. 009). Kaplan-Meier survival analysis showed that Tim3 expression in colorectal cancer and in TILs was significantly associated with patient overall survival (OS) rate (P=0. 039, and 0. 001). Tim3 may be a potential prognostic marker and a therapy target for colorectal cancer.
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