Bao Shixiang, Jiang Xiaopei, Jin Shuai, Tu Peipei, Lu Jingtao
School of Life Sciences, Anhui Medical University, Hefei, China.
Front Oncol. 2021 Jun 25;11:694145. doi: 10.3389/fonc.2021.694145. eCollection 2021.
Primary liver cancer (PLC) is one of the most common types of cancer worldwide. Hepatocellular carcinoma (HCC) accounts for approximately 90% of PLC cases. The HCC microenvironment plays an important role in the occurrence and development of HCC. Immunotherapy for the HCC microenvironment has become an effective treatment strategy. T lymphocytes are an important part of the HCC microenvironment, and programmed cell death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are the main immunosuppressive molecules of T lymphocytes. Transforming growth factor β1 (TGF-β1) can inhibit the immune function of T lymphocytes and promote the occurrence and development of tumors. However, few studies have explored whether TGF-β1 can upregulate the expression of PD-1 and CTLA-4 on T cells. In this study, we showed that TGF-β1 upregulated the expression of PD-1 and CTLA-4 on T lymphocytes and attenuated the cytotoxicity of T lymphocytes for HCC cells and . In addition, TGF-β1 increased the apoptosis of T lymphocytes induced by HCC cells. Finally, we found that the mechanism by which TGF-β1 upregulates the expression of PD-1 and CTLA-4 on T lymphocytes may be related to the calcineurin-nuclear factor of activated T cells 1 (CaN/NFATc1) pathway. This study will provide some experimental basis for liver cancer immunotherapy based on the tumor microenvironment.
原发性肝癌(PLC)是全球最常见的癌症类型之一。肝细胞癌(HCC)约占PLC病例的90%。HCC微环境在HCC的发生和发展中起重要作用。针对HCC微环境的免疫疗法已成为一种有效的治疗策略。T淋巴细胞是HCC微环境的重要组成部分,程序性细胞死亡蛋白1(PD-1)和细胞毒性T淋巴细胞相关抗原4(CTLA-4)是T淋巴细胞的主要免疫抑制分子。转化生长因子β1(TGF-β1)可抑制T淋巴细胞的免疫功能,促进肿瘤的发生和发展。然而,很少有研究探讨TGF-β1是否能上调T细胞上PD-1和CTLA-4的表达。在本研究中,我们发现TGF-β1上调了T淋巴细胞上PD-1和CTLA-4的表达,并减弱了T淋巴细胞对HCC细胞的细胞毒性。此外,TGF-β1增加了HCC细胞诱导的T淋巴细胞凋亡。最后,我们发现TGF-β1上调T淋巴细胞上PD-1和CTLA-4表达的机制可能与钙调神经磷酸酶-活化T细胞核因子1(CaN/NFATc1)途径有关。本研究将为基于肿瘤微环境的肝癌免疫治疗提供一些实验依据。