胃癌与CD8+T细胞的表型和功能衰竭有关。另一方面，已知Toll样受体（TLR）激动剂在癌症免疫治疗中作为佐剂使用时能够增强免疫反应。由于炎性通路信号的损害通常与T细胞耗竭有关，本研究的目的是评估多肌苷多胞核苷酸酸（poly (I:C)）介导的TLR3激活对浸润肿瘤CD8+T细胞的正常表型和功能恢复的影响。体外处理了35例胃癌患者的外周血和肿瘤浸润CD8+T细胞，使用逐渐增加的多（I:C）浓度，并检测这些细胞上程序死亡-1（PD-1）和淋巴细胞激活基因3（LAG3）的表达。与年龄相匹配的健康对照组相比，胃癌患者的外周CD8+T细胞表达PD-1和LAG3较高，且增殖较低。使用100μg / mL浓度的多（I:C）体外处理CD8+T细胞可以减轻外周和肿瘤浸润CD8+T细胞上PD-1和LAG3抑制性检查点分子的表达。所述剂量的多（I:C）改善了CD8+T细胞对多克隆活化剂的增殖反应。此外，多（I:C）处理的CD8+T细胞释放的干扰素γ（IFN-γ）和肿瘤坏死因子α（TNF-α）增加。多（I:C）表现出潜力减少外周和肿瘤浸润的CD8+T细胞的表型和功能衰竭，并导致它们进行更多的增殖和细胞因子释放。© 2023年。作者，独家授权给Springer-Verlag GmbH Germany，属于Springer Nature的一部分。

Gastric cancer is associated with the phenotypic and functional exhaustion of TCD8+ cells. On the other hand, Toll-like receptor (TLR) agonists are known to reinforce immune responses when used as adjuvants in cancer immunotherapies. Since the compromised signaling of pro-inflammatory pathways is usually associated with T cell exhaustion, the aim of the present study was to evaluate the impact of polyinosinic-polycytidylic acid (poly (I:C))-mediated TLR3 activation in restoring the normal phenotype and function of tumor-infiltrating TCD8+ cells. Peripheral blood and tumor-infiltrating TCD8+ cells of 35 gastric cancer patients were in vitro treated with increasing concentrations of poly (I:C) and the expressions of programmed death-1 (PD-1) and lymphocyte-activation gene 3 (LAG3) on these cells were examined. The peripheral TCD8+ cells of gastric cancer patients showed higher expressions of PD-1 and LAG3 along with lower proliferation compared to TCD8+ cells of the age-matched healthy control individuals. The in vitro treatment of TCD8+ cells with 100 μg/mL concentration of poly (I:C) alleviated the expression of PD-1 and LAG3 inhibitory checkpoint molecules on both peripheral and tumor-infiltrating TCD8+ cells. The mentioned dose of poly (I:C) improved the proliferation of TCD8+ cells in response to a polyclonal activator. Besides, the releases of Interferon gamma (IFN-γ) and Tumor necrosis factor alpha (TNF-α) were increased in the poly (I:C)-treated TCD8+ cells. Poly (I:C) demonstrated a potential to reduce the phenotypic and functional exhaustion of the peripheral and tumor-infiltrating TCD8+ cells and caused them to undergo more proliferation and cytokine release.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.