Circulating antigen-primed cytotoxic T-cells in patients with renal tumors treated with surgery

Introduction: Systemic immunotherapy has changed the paradigm of treatment of advanced renal cell carcinoma, but nephrectomy continues to benefit selected patients. While we continue to identify mechanisms behind drug resistance, the effect of surgery on natural anti-tumor immunity is poorly understood. Specifically, peripheral blood mononuclear cell (PBMC) profile and tumor reactive cytotoxic T lymphocytes changes secondary to tumor resection have not been extensively characterized. Hence, we aimed to evaluate the effect of nephrectomy on PMBC profile and circulating antigen-primed CD8+ T-cells for patients undergoing solid renal mass resection.

Methods: Patients with localized or metastatic solid renal masses who underwent nephrectomy from 2016 to 2018 were enrolled. Blood samples were collected at 3 timepoints for PBMCs analysis (pre-op, 1 day, and 3 months post-op). Flow cytometry was used to identify CD11a^high CD8+ T lymphocytes that were then further characterized according to the expression of CX3CR1/GZMB, Ki67, Bim, and PD-1. Changes in circulating CD8+ T-cells from pre-op to 1 day and 3 months post-op were evaluated using Wilcoxon signed rank tests.

Results: Antigen-primed CX3CR1+GZMB+ T-cells significantly increased by 3 months after surgery among patients with RCC (0.8 × 10⁹ cells; P = 0.01). In contrast, there was a decrease in absolute numbers of Bim+ T-cells at 3 months (-1.9 × 10⁹ cells; P = 0.02). There were no significant absolute changes in PD-1+ (-1.4 × 10⁹; P = 0.7) and CD11a^high CD8+ T lymphocytes (1.3 × 10⁹; P = 0.9). Ki67+ T-cells decreased by 3 months (-0.8 × 10⁹; P < 0.001).

Conclusions: Nephrectomy is associated with an increase in cytolytic antigen-primed CD8+ T-cells and specific PBMC profile changes. Further studies are warranted to ascertain the role surgery may have in the restoration of anti-tumor immunity.