Early-like differentiation status of systemic PD-1⁺CD8⁺ T cells predicts PD-1 blockade outcome in non-small cell lung cancer.

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⁺, T_EEM) to PD-1⁺ effector CD8⁺ T cells (CD28^-CD27^-CD45RO^-, T_E) 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 T_EEM 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.

SUBMITTER: Khanniche A 

PROVIDER: S-EPMC9327560 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature