Role of Immunotherapy in the Management of Locally Advanced and Recurrent/Metastatic Cervical Cancer

Abstract

Despite combined therapeutic approaches, there is an unmet clinical need to identify effective strategies for improved patient outcomes in treating locally advanced and metastatic cervical cancer (CC). Immunotherapy is emerging as a novel therapeutic approach in this disease for which the causative agent, human papillomavirus (HPV), has dynamic, complex immunomodulatory effects. This review explores the biologic rational of immuno-oncology in the treatment of CC and discusses the initial clinical efficacy, ongoing clinical trials, and rationale for combined multimodal treatment approaches for locally advanced and recurrent/metastatic CC. The utility of immune checkpoint inhibitors is explored, including anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4), PD-1, and PD-L1. Preliminary data supporting the combination of radiotherapy and immunotherapy and areas of active drug development for CC are also reviewed.

Comprehensive Analysis of the Relationships Between Tumor Mutation Burden With Immune Infiltrates in Cervical Cell Carcinoma

“…At present, there are many clinical trials of immunosuppressive agents in the treatment of CCC, but most of them have not been started for long, and all of them are in phase I or phase II of the trial, and there are not many clinical trials that publish results ( Duska et al, 2017 ; Frenel et al, 2017 ; Hollebecque et al, 2017 ; Mayadev et al, 2017 ; Lheureux et al, 2018 ). The predictive markers of immunotherapy are the focus of clinicians and patients, but in the clinical trials of immunotherapy for CCC, there are no other markers related to the efficacy of immunotherapy except Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) and programmed cell death receptor-1 (PD-1) ( Dyer et al, 2019 ). Tumor mutation burden (TMB) is becoming a new biomarker, especially predicting the response to PD-L1 therapy.…”

Anti-PD-L1 (atezolizumab) as an immune primer and concurrently with extended-field chemoradiotherapy for node-positive locally advanced cervical cancer

“…Immunotherapy added to radiation is promising in the field of oncology for synergistic effects, and the opportunity to study this combination in cervical cancer is the basis for the clinical trial NRG Oncology GY017, ‘ Anti PD-L1 ( A tezolizumab) as an Immune Primer and Concurrently with Extended Field Chemoradiotherapy for Node Positive Locally Advanced Cervical Cancer’. 2…”

Integrative Bioinformatics Approaches to Screen Potential Prognostic Immune-Related Genes and Drugs in the Cervical Cancer Microenvironment

“…Their interaction played critical a role in tumor immune escape (Antoni, 2012). Monoclonal antibodies targeting PD-1/programmed death ligand, such as pembrolizumab, have already been widely assessed in clinical trials and are currently approved for the treatment of advanced cervical cancer (Borcoman and Le Tourneau, 2017;Chen et al, 2017;Chung et al, 2019;Dyer et al, 2019). Interestingly, in our results, higher expression of PD-1 was associated with better clinical outcomes.…”