Immune and Inflammation: Related Factor Alterations As Biomarkers for Predicting Prognosis and Responsiveness to PD-1 Monoclonal Antibodies in Cervical Cancer

Purpose: We aimed to elucidate the potential mechanisms of effective responsiveness to PD-1 monoclonal antibody and evaluate more reliable biomarkers to improve the ability to predict the populations of cervical cancer (CC) suitable for immunotherapy.

Methods: Peripheral blood samples of CC patients undergoing anti-PD-1 therapy were collected before and after treatment. Differentially expressed genes (DEGs) were analyzed between partial response (PR) and progressive disease (PD) patients. A novel prognostic inflammation and immune-related response gene (IRRG) model was constructed and its prognostic role, correlation with tumor immunity and tumor mutation were evaluated.

Results: DEGs in PR patient after treatment could predict the response to PD-1 monoclonal antibodies. Among PR-specific pathways, tumor immunity, leukocyte migration, and cytokine activities were prominently enriched. Additionally, an IRRG signature comprising CTLA4, AZU1, C5, LAT, CXCL2, GDF7, MPL, PPARG and CELA1 was established and validated to predict the prognosis of CC with great accuracy and specificity. This signature could reflect the tumor microenvironment (TME) and tumor mutational burden (TMB). We also found stimulated adaptive immunity and downregulated inflammation at baseline in patients with sensitive responses to PD-1 monoclonal antibody.

Conclusion: We developed an IRRG signature and verified that it was an independent prognostic factor for predicting survival and could reflect a sensitive response to PD-1 monoclonal antibody, which plays a nonnegligible role in the TME of CC. Further investigations are warranted to confirm that patients with stimulated adaptive immunity and downregulated inflammation at baseline could achieve a better survival benefit from PD-1 monoclonal antibody.