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

Asma Khanniche; Yi Yang; Jie Zhang; Shiqing Liu; Liliang Xia; Huangqi Duan; Yaxian Yao; Bingrong Zhao; Guo-Ping Zhao; Chengping Hu; Ying Wang; Shun Lu

doi:10.1002/cti2.1406

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

Clin Transl Immunology. 2022 Jul 27;11(7):e1406. doi: 10.1002/cti2.1406. eCollection 2022.

Authors

Asma Khanniche^{1

2}, Yi Yang³, Jie Zhang³, Shiqing Liu⁴, Liliang Xia³, Huangqi Duan¹, Yaxian Yao³, Bingrong Zhao⁴, Guo-Ping Zhao², Chengping Hu⁴, Ying Wang¹, Shun Lu³

Affiliations

¹ Department of Immunology and Microbiology, Shanghai Institute of Immunology Shanghai Jiao Tong University School of Medicine Shanghai China.
² Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen China.
³ Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital Shanghai Jiao Tong University Shanghai China.
⁴ Department of Respiratory Medicine, Xiangya Lung Cancer Center, Xiangya Hospital Central South University Changsha China.

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.

Keywords: PD‐1 blockade; T cells; biomarkers; early‐like differentiation; non‐small‐cell lung cancer.