肿瘤突变产生的新抗原是T细胞免疫治疗的重要靶点，免疫检查点阻断已被批准用于治疗多种实体瘤。我们研究了在小鼠模型中采用养成性新抗原反应性T细胞（NRT）和编程细胞死亡蛋白1抑制剂（抗PD1）联合治疗肺癌的潜在好处。NRT细胞是通过共培养T细胞和新抗原RNA疫苗诱导的树突状细胞制备的。然后，将养成性NRT细胞与抗PD1联合使用，应用于带肿瘤荷瘤的小鼠。前后治疗的细胞因子分泌、抗肿瘤功效和肿瘤微环境（TME）变化进行了体外和体内评估。我们成功基于本研究确定的5个新抗原表位产生了NRT细胞。NRT细胞在体外表现出增强的细胞毒性表型，而联合治疗则导致肿瘤生长减弱。此外，这种联合策略还降低了肿瘤浸润性T细胞上PD-1抑制标志的表达，促进了肿瘤特异性T细胞向肿瘤部位的转移。在联合应用抗PD1疗法的情况下，养成性NRT细胞的移植具有抗肿瘤作用，是治疗实体瘤的可行、有效和新颖的免疫治疗方案。© 2023年，作者（们）在Springer-Verlag GmbH Germany的排他许可下，Springer Nature的一部分。

Neoantigens produced from mutations in tumors are important targets of T-cell-based immunotherapy and immune checkpoint blockade has been approved for treating multiple solid tumors. We investigated the potential benefit of adoptive neoantigen-reactive T (NRT) cells in combination with programmed cell death protein 1 inhibitor (anti-PD1) for treating lung cancer in a mouse model.NRT cells were prepared by co-culturing T cells and neoantigen-RNA vaccine-induced dendritic cells. Then, adoptive NRT cells in combination with anti-PD1 were administered to tumor-bearing mice. Pre- and post-therapy cytokine secretion, antitumor efficacy, and tumor microenvironment (TME) changes were determined both in vitro and in vivo.We successfully generated NRT cells based on the 5 neoantigen epitopes identified in this study. NRT cells exhibited an enhanced cytotoxic phenotype in vitro and the combination therapy led to attenuated tumor growth. In addition, this combination strategy downregulated the expression of the inhibitory marker PD-1 on tumor-infiltrating T cells and promoted the trafficking of tumor-specific T cells to the tumor sites.The adoptive transfer of NRT cells in association with anti-PD1 therapy can exert an antitumor effect on lung cancer, and is a feasible, effective, and novel immunotherapy regimen for treating solid tumors.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.