肿瘤细胞治疗研究
英文原题：Tumor-infiltrating T lymphocytes: A promising immunotherapeutic target for preventing immune escape in cholangiocarcinoma.
Tumor-infiltrating T lymphocytes: A promising immunotherapeutic target for preventing immune escape in cholangiocarcinoma.
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胆管癌（CCA）在全球日益常见且致死率高。肿瘤浸润T细胞亚型各自对免疫系统发挥不同作用，共同构成CCA肿瘤微环境（TME）的重要部分。调节性T细胞（Treg）通过分泌细胞因子和其他物质降低活化T细胞应答，发挥免疫抑制作用。CD8+ T细胞活化减少会刺激程序性死亡蛋白1（PD-1），破坏T淋巴细胞免疫稳态。另一方面，活化的细胞毒性T淋巴细胞（CTL）可经穿孔素-颗粒酶或Fas-FasL通路清除癌细胞。T细胞也有助于Th1和CTL免疫细胞浸润恶性肿瘤。CD8+ T细胞浸润通常提示较好预后，而生存与Treg密度呈负相关。单用或联合免疫检查点抑制剂为CCA免疫治疗提供新策略。此外，新的免疫靶点发现、多种检查点抑制剂联合及CAR-T 等免疫疗法，有望提高抗CCA治疗效果并减少不良反应。
Cholangiocarcinoma (CCA) is becoming more common and deadly worldwide. Tumor-infiltrating T cell subtypes make distinct contributions to the immune system; collectively, they constitute a significant portion of the tumor microenvironment (TME) in CCA. By secreting cytokines and other chemicals, regulatory T cells (Tregs) decrease activated T cell responses, acting as immunosuppressors. Reduced CD8 + T cell activation results in stimulating programmed death-1 (PD-1), which undermines the immunological homeostasis of T lymphocytes.
On the other hand, cancer cells are eliminated by activated cytotoxic T lymphocyte (CTL) through the perforin-granzyme or Fas-FasL pathways. Th1 and CTL immune cell infiltration into the malignant tumor is also facilitated by T cells. A higher prognosis is typically implied by CD8 + T cell infiltration, and survival is inversely associated with Treg cell density. Immune checkpoint inhibitors, either singly or in combination, provide novel therapeutic strategies for CCA immunotherapy.
Furthermore, it is anticipated that immunotherapeutic strategies-such as the identification of new immune targets, combination treatments involving several immune checkpoint inhibitors, and chimeric antigen receptor-T therapies (CAR-T)-will optimize the effectiveness of anti-CCA treatments while reducing adverse effects.
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