Dynamic changes of lymphocyte subsets during multimodal treatment of patients with inoperable stage III NSCLC.

Abstract

e21011 Background: Lymphocytopenia is associated with deterioration of patient survival in solid cancers treated with concurrent chemo/radiotherapy (cCRT). A prospective analysis of peripheral blood mononuclear cells during cCRT in inoperable stage III NSCLC patients was performed to determine dynamic changes of individual lymphocyte subsets. Methods: Twenty-one patients were prospectively enrolled in this study. Eighteen patients received platinum-based cCRT, seven of them received, additionally, concurrent and/or sequential immune checkpoint-inhibition (ICI). Thoracic irradiation (TRT) was delivered with median total dose of 62Gy (31 daily fractions of 2Gy) in all patients. Peripheral blood was collected 5-10 days before treatment (A1), three weeks after start of cCRT (A3), on the last day of TRT (RTend) and during follow-up. Samples were analyzed using polychromatic flow cytometry. Results are reported for time-points A1, A3 and RTend. Results: Sixteen patients met final analysis criteria, 50% of them received concurrent and/or sequential ICI. All patients developed severe lymphocytopenia; in 81% of them lymphocyte nadir was documented at A3. Lymphocyte subsets, B cells, T cells (CD4, CD8), regulatory T cells, and NK cells, decreased with medians between 99.9% and 59%. Lymphocyte nadir was independent of the absolute numbers of immune cells that a patient had before start of cCRT or whether additional ICI was applied. From A3 to RTend, all lymphocyte subsets started to recover in patients treated with cCRT alone, while they remained low in patients who received additional ICI. The ratios of CD4/CD8 and CD8/Treg cells did not change during treatment (A1 to RTend) and was not different between the patients treated with or without ICI. However, the fraction of PD-1 cells among CD8 T-cells decreased in patients treated with ICI and remained low until RTend (range 0.55%-13.8%). In contrast, in 50% of patients treated with cCRT alone, PD-1 T-cell among CD8 T-cells increased and remained high (range 6.8%-46.3%) until RTend. Conclusions: Delayed recovery of lymphocyte subsets in peripheral blood was observed in patients treated with cCRT combined with concurrent or sequential ICI. A decrease of PD-1 T-cells among CD8 T-cells was described exclusively in patients treated with additional ICI.