METHODS: The retrospective analysis was conducted on the clinical records of 115 metastatic clear cell renal cell carcinoma (mccRCC) patients treated with anti-PD-1 antibody plus Axitinib between March 2020 and June 2023. Observation target: objective response rate (ORR), and overall survival (OS), progression-free survival (PFS) and immune profile.
RESULTS: Patients with high TIBs portended lower ORR of the combination therapy (p = 0.033). TIBs was an independent predictor for poorer OS (p = 0.013) and PFS (p = 0.021) in mccRCC patients with combination treatment. TIBs infiltration was associated with more CD4+T (p < 0.001), CD8+T (p < 0.001), M2 macrophages (p = 0.020) and regulatory T cells (Tregs) (p = 0.004). In TIBs high patients, the percentages of PD-1, CTLA-4 and TIM-3 positive rate were significantly increased in CD4+T (p = 0.038, 0.029 and 0.002 respectively) and CD8+T cells (p = 0.006, 0.026 and < 0.001 respectively).
CONCLUSIONS: Our study revealed TIBs infiltration predicted adverse outcomes in mccRCC patients treated with anti-PD-1 antibody plus Axitinib. As a corollary, TIBs positively associated with M2 macrophages and Tregs, leading to subsequent multiple immune checkpoints related exhaustion of T cells. Thus, only PD-1 blockade are inadequate to reverse T cells exhaustion effectively in high TIBs mccRCC patients.
方法:对2020年3月至2023年6月期间接受抗PD-1抗体联合阿西替尼治疗的115例转移性透明细胞肾细胞癌(mccRCC)患者的临床记录进行回顾性分析。观察目标:客观反应率(ORR),和总生存率(OS),无进展生存期(PFS)和免疫谱。
结果:高TIB患者预示联合治疗的ORR较低(p=0.033)。TIB是联合治疗mccRCC患者OS(p=0.013)和PFS(p=0.021)较差的独立预测因子。TIBs浸润与更多的CD4+T相关(p<0.001),CD8+T(p<0.001),M2巨噬细胞(p=0.020)和调节性T细胞(Tregs)(p=0.004)。在TIBs高患者中,CD4+T细胞(p=0.038、0.029和0.002)和CD8+T细胞(p=0.006、0.026和<0.001)中PD-1、CTLA-4和TIM-3阳性率显著升高。
结论:我们的研究显示TIBs浸润预测了抗PD-1抗体联合阿西替尼治疗mccRCC患者的不良结局。作为一个推论,TIB与M2巨噬细胞和Tregs呈正相关,导致随后的多个免疫检查点相关的T细胞耗尽。因此,仅PD-1阻断不足以有效逆转高TIBsmccRCC患者的T细胞耗竭。