Abstract 5198: Dynamics of circulating immune cells during chemoradiotherapy in patients with locally advanced non-small cell lung cancer support earlier administration of anti-PD-1/PD-L1 therapy

Abstract Background: Chemoradiotherapy (CRT) followed by consolidation immune checkpoint inhibitors (ICIs) significantly improves survival in unresectable locally advanced non-small cell lung cancer (LA-NSCLC). However, the optimal sequence for CRT and ICIs has not yet been established. We investigated the dynamics of peripheral blood immune cells during CRT to determine the best sequence for treatment. Methods: Peripheral blood samples were prospectively collected pre-treatment, weekly during CRT for 6 weeks, and 1 month post-treatment in 24 patients with LA-NSCLC who received definitive CRT. Immune cell analysis was performed by flow cytometry. Ex vivo PD-1 blockade assays were performed by IFN-γ intracellular cytokine staining. Results: Lymphopenia was prominently observed during CRT and mostly recovered 1 month post-CRT. Robust proliferation of CD8+ T cells was induced, peaking in the last week during CRT and decreasing post-CRT. The robust proliferation of CD8+ T cells led to an increase in the frequency of CD28-CD57+ replicative senescent and terminally differentiated cells post-CRT. Tumor-reactive CD8+ T cells increased during CRT and peaked in the last week. One month post-CRT, the frequency of tumor-reactive CD8+ T cells decreased and TOXhiTCF1lo terminally exhausted CD8+ T cells significantly increased. Anti-PD-1-induced functional restoration of PD-1+CD8+ T cells was maximized in the last week of CRT and significantly decreased post-CRT. Conclusions: The findings suggest that earlier administration of PD-1 blockade may be associated with superior efficacy compared to delayed administration after completion of CRT. These findings provide an immunological rationale for optimal timing of combining ICIs with CRT in clinical trials. Citation Format: Kyung Hwan Kim, Hongryull Pyo, Dongryul Oh, Jae Myoung Noh, Yong Chan Ahn, Hong In Yoon, Jiyun Lee, Sehhoon Park, Hyun-Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Bo Mi Ku, Myung-Ju Ahn, Eui-Cheol Shin. Dynamics of circulating immune cells during chemoradiotherapy in patients with locally advanced non-small cell lung cancer support earlier administration of anti-PD-1/PD-L1 therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5198.