238P Exploring blood immune cell dynamics to unravel the immunomodulatory effect of radiotherapy in NSCLC patients undergoing immune checkpoint inhibitors

The role of radiotherapy (RT) in immunotherapy-based (IO) combinatory approaches to advanced NSCLC is still uncertain due its dual immune -suppressive and -stimulatory effect. We performed a longitudinal peripheral blood (PB) analysis determine whether RT, by affecting cell phenotypes dynamics, impacts on clinical outcome IO-treated patients. PB samples were prospectively collected at baseline (T0) first disease assessment (T1) stage IV undergoing 1st line IO-based regimens alone (RTnull) or combined with RT (RTpre, within 4 weeks before IO; RTpost, during IO). Flow cytometric included CD3, CD8, CD4, NK, NKT, CD19, CD14 Treg cells, expression functional molecules (PD1, Granzyme B [GZB], Perforin [Perf]) proliferative index (Ki67). parameters their delta variation ([T1-T0/T0] * 100) correlated administration, Objective Response Rate (ORR) Progression-free survival (PFS). Among 57 patients, 22 underwent either 32%) (RTpost, 68%) IO. doses ranged from 8 54 Gy according sites involvement. No significant differences IO response emerged between RTnull cases. Compared RTnull, RTpre profiles exhibited increased % NK cells expressing PD1, reduced CD4+GZB/Perf+ Tregs. Delta revealed that attenuated the downregulation PD1 CD4 CD19 following IO, favored circulating release GZB/Perf+ CD8 CD4. RTpost number, proliferation expression, while increasing NKT. At variance RTpre, did not affect PD1+ T kinetic, although decreased total NKs. observed clear trend towards prolonged PFS group (median PFS: RTpre= reached, RTpost= 7.1 mos, RTnull= 5.9 mos) associated slightly ORR, hinting positive cytotoxic (CD8+GZB/Perf+, NK) suppressive (Tregs) balance triggered may result greater benefit timing differentially impact patients shaping dynamics.