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Hypofractionated radiotherapy (HFRT) or chemotherapy combined with programmed death-1 (PD-1) blockade has achieved good clinical control in advanced nonsmall cell lung cancer (NSCLC). However, the relative influence of HFRT + PD-1 blockade and chemo-immunotherapy on peripheral memory T cell subsets in NSCLC responders has not been evaluated in clinical practice. Thirty-nine patients with advanced NSCLC were enrolled. The frequencies of naive (Tn; CD45RA+CCR7+), central memory (Tcm; CD45RA–CCR7+), effector memory (Tem; CD45RA–CCR7–), and effector memory RA (TemRA; CD45RA+CCR7–) T cell subsets and PD-1 expression were analyzed in CD4+ and CD8+ T cells using flow cytometry from peripheral blood samples. The correlations of memory T cell subsets and PD-1 expression with overall survival in HFRT + PD-1 blockade group were examined using the Kaplan–Meier method. Patients with partial response to HFRT + PD-1 blockade showed reduction in Tn and expansion in TemRA cell subpopulations among CD8+ T cells and reduced PD-1+CD4+ and PD-1+CD8+ T cells, all of which were significantly correlated with overall survival. The responders to chemo-immunotherapy showed expansion of the TemRA and decrease of Tcm in CD8+ T cell subpopulation. Our findings show that HFRT+PD-1 blockade and chemo-immunotherapy combination therapies induce differential memory T cell subset differentiation, offering predictive markers for treatment response. Clinical Trial Information: https://clinicaltrials.gov/ct2/show/ChiCTR-1900027768. [ABSTRACT FROM AUTHOR]