Efficacy of PD-1 blockade in cervical cancer is related to a CD8⁺FoxP3⁺CD25⁺ T-cell subset with operational effector functions despite high immune checkpoint levels.

ABSTRACT:

Background

Cervical cancer (CxCa) is mainly a locally invading disease that metastasizes to loco-regional lymph node basins before involving distant organs in more advanced stages. Local immune potentiation of tumor-draining lymph nodes (TDLN) may thus protect against tumor progression.

Methods

To identify therapeutic targets for local immune modulation, multi-parameter flow cytometric T-cell profiling of primary cervical tumors (PT) and TDLN (n = 37) was performed. The in-vitro effect of PD-1 blockade on T-cell reactivity to HPV16 E6 oncoproteins was determined in cultures of TDLN and PT single cell suspensions (n = 19). Also, intracellular cytokine staining (ICS) upon anti-CD3 stimulation was performed in metastatic TDLN (LN+) and PT (n = 7), as well as multiplexed immunof

SUBMITTER: Heeren AM 

PROVIDER: S-EPMC6373123 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature