Purpose Immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) has become first-line therapy for metastatic renal cell carcinoma patients. This study aims to investigate the effect of tumor infiltrating B lymphocytes (TIBs) on the combination therapy. 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 M 2 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.
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Lin et al. (2024) studied this question.
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