Multiparametric immune profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: an exploratory study of the CLAP trial

Abstract

Purpose: Checkpoint immunotherapy is a promising treatment option for advanced cervical cancer. To aid in selecting patients for this treatment, we identified potential predictors of the response to anti-PD-1 combination therapy.

Methods: We simultaneously characterized CD8⁺, FoxP3⁺, PD-L1⁺, CD68⁺, CD31⁺, PANCK⁺, and PANCK^-PD-L1⁺ cells at the invasive margin (IM) of tumor by multispectral imaging of tissue sections from 37 patients with advanced cervical cancer in our previous trial cohort. The densities of each cell and cell-to-cell topography were compared between the responder and non-responder groups and evaluated for their predictive value in clinical response and survival.

Results: CD8⁺ T cells, PD-L1⁺ cells, and PANCK^-PD-L1⁺ immune cells showed higher densities at the IM in the responders than in the non-responders (P = 0.022, 0.0094, and 0.049, respectively). A higher density of CD8⁺ T cells at the IM was related to prolonged progression-free survival (PFS; P = 0.031). A higher ratio of CD68⁺/CD8⁺ cells was found in the non-responder group (P = 0.003) and related to poor PFS (P = 0.016). A higher density of PANCK^-PD-L1⁺ immune cells within 20, 30, and 45 µm of PANCK⁺ tumor cells was correlated with better clinical response (P = 0.017, 0.017, and 0.02, respectively).

Conclusions: Multiparametric immune profiling of CD8⁺ T cells, PD-L1⁺ cells, CD68⁺ macrophages and PANCK^-PD-L1⁺ immune cells at the invasive margin may help identify patients with cervical cancer who may benefit from anti-PD-1 combination therapy.

Clinical trial registration: ClinicalTrials. gov identifier: NCT03816553, January 25, 2019.

Keywords: Cervical cancer; Immunotherapy; Multiparametric immune; Tumor-infiltrating lymphocyte.