Early‐like differentiation status of systemic PD‐1+CD8+ T cells predicts PD‐1 blockade outcome in non‐small cell lung cancer. Issue 7 (27th July 2022) - Khanniche, Asma
Abstract: Objectives: Despite remarkable advances in the treatment of non‐small cell lung cancer (NSCLC) with anti‐programmed death (PD)‐1 therapy; only a fraction of patients derives durable clinical benefit. In this study, we investigated whether the differentiation status of systemic CD8 + T cells predicts the outcome of PD‐1 blockade in NSCLC. Methods: We carried out a prospective study on a total of 77 NSCLC patients receiving anti‐PD‐1 blockers, among which 47 patients were assigned as a discovery cohort and 30 patients as a validation cohort. Peripheral blood samples were obtained at baseline and upon multiple therapy cycles and analyzed by multi‐parameter flow cytometry. Results: We found that a higher baseline ratio of PD‐1 + early effector memory CD8 + T cells (CD28 + CD27 − CD45RO +, TEEM ) to PD‐1 + effector CD8 + T cells (CD28 − CD27 − CD45RO −, TE ) delineated responders to PD‐1 blockade from progressors and was associated with prolonged progression‐free survival (PFS) and durable clinical benefit. Moreover, PD‐1 + CD8 TEEM cells exhibited early responses after anti‐PD‐1 therapy and was the major fraction of cycling PD‐1 + Ki67 + CD8 + T cells to expand specifically with positive impact on PFS. Conclusion: These findings provide insights into how the baseline differentiation status of the peripheral immune system determines responses to PD‐1‐targeted therapies. Abstract : In this study, we examined the association between PD‐1 blockade and the differentiation status of systemic CD8 T‐cell immunity in non‐small cell lung cancer. We found that early‐like differentiation status of PD‐1 + CD8 T cells is associated with favorable outcome to PD‐1‐targeted immunotherapy. We further identified a baseline indicator of response to immune checkpoint blockade for implementation in clinical practice.