Comprehensive longitudinal immune cell monitoring in patients with extensive-stage small-cell lung cancer patients treated with chemo-immunotherapy to predict early relapse.

Abstract

8096 Background: Small cell lung cancer (SCLC) is characterized by rapid growth, and although initial chemo-immunotherapy achieves high response rates, relapse typically occurs within 6–12 months. Emerging data suggest that myeloid-derived suppressor cells (MDSCs) and lymphocyte subsets influence immunotherapy response and relapse kinetics. We conducted a detailed immune profiling study to characterize circulating myeloid and lymphoid populations in SCLC patients, comparing those with early vs. late (>200 days) relapse. Methods: Purified PBMCs collected at baseline and relapse were analyzed by high-parameter flow cytometry using panels containing myeloid and lymphocytic markers. Results: Patients with ES-SCLC treated with chemo-immunotherapy were prospectively enrolled in this biomarker trial. A total of 32 were accrued. Among patients with early (<200 days) vs. late (≥200 days) relapse, baseline frequencies of CD33+ myeloid cells were similar. At relapse, however, a marked decrease in activated CD15+/CD16+ neutrophils was observed in both groups. PMN-MDSCs showed distinct kinetics: early-relapse patients had elevated MDSCs at baseline, whereas late-relapse patients exhibited significant MDSC expansion only at relapse. Additionally, a P-selectin–high monocytic subpopulation (M-MDSC) emerged more prominently in the late-relapse cohort, potentially reflecting a protective or anti-tumor phenotype. On lymphocyte analysis, a significant decline in CD8+ cytotoxic T-cell frequencies was observed at relapse across all patients, indicating a potential mechanism of immune evasion. The analysis of CD107 expression further supported the decrease in cytotoxic T-cell activity at relapse. Notably, higher baseline frequencies of CD57+ T-cell correlated with relapse-free intervals greater than 200 days. Lastly, lower baseline frequencies of activated B cells were associated with longer relapse-free survival. Conclusions: Our results reveal novel findings, suggesting that unique kinetics of myeloid and lymphoid immunophenotype levels are associated with relapse timing in SCLC treated with chemo-immunotherapy. These findings suggest potential predictive biomarkers and inform the development of targeted immunomodulatory strategies.