The elevated expression of immune checkpoints by the tumor microenvironment is associated with poor prognosis in several cancers due to the exhaustion of tumor-infiltrating lymphocytes (TILs), and the effective suppression of the expression of these genes is key to reversing the exhaustion of TILs. Herein, we determined that serine/arginine-rich splicing factor 2 (SRSF2) is a target for blocking the tumor microenvironment-associated immunosuppressive effects. We found that the expression of SRSF2 was increased in exhausted T cells and that SRSF2 was involved in multiple immune checkpoint molecules mediating TILs’ exhaustion. Furthermore, SRSF2 was revealed to regulate the transcription of these immune checkpoint genes by associating with an acyl-transferases P300/CBP complex and altering the H3K27Ac level near these genes, thereafter influencing the recruitment of signal transducer and activator of transcription 3 (STAT3) to these gene promoters. Collectively, our data indicated that SRSF2 functions as a modulator of the anti-tumor response of T cells and may be a therapeutic target for reversing the exhaustion of TILs.

由于肿瘤浸润淋巴细胞（TIL）的耗尽，肿瘤微环境中免疫检查点表达的升高与预后不良有关，而有效抑制这些基因表达是逆转TIL耗尽的关键。在这里，我们确定富含丝氨酸/精氨酸的剪接因子2（SRSF2）是阻断肿瘤微环境相关的免疫抑制作用的目标。我们发现SRSF2的表达在疲惫的T细胞中增加，并且SRSF2参与了介导TIL疲惫的多个免疫检查点分子。此外，还发现SRSF2通过与酰基转移酶P300 / CBP复合物相关联并改变这些基因附近的H3K27Ac水平来调节这些免疫检查点基因的转录，此后影响信号转导子和转录激活子3（STAT3）向这些基因启动子的募集。总体而言，我们的数据表明SRSF2充当T细胞抗肿瘤应答的调节剂，并且可能是逆转TIL衰竭的治疗靶标。