# Overcoming immune resistance in ovarian cancer: checkpoint inhibitors, tumor microenvironment, and translational advances

## TL;DR

This review discusses the challenges and recent progress in using immune checkpoint inhibitors for treating ovarian cancer, focusing on improving response rates and overcoming resistance.

## Contribution

The paper provides a comprehensive overview of current ICI-based therapies, biomarkers, and translational advances in ovarian cancer immunotherapy.

## Key findings

- Monotherapy with ICIs shows low response rates in ovarian cancer.
- Combination therapies with ICIs and other agents show promise in biomarker-selected populations.
- Immune resistance and an immunosuppressive tumor microenvironment remain major barriers to effective treatment.

## Abstract

Ovarian cancer remains one of the most lethal gynecologic malignancies, with high recurrence rates and poor prognosis, particularly in platinum-resistant cases. Immune checkpoint inhibitors (ICIs), especially those targeting PD-1/PD-L1, have demonstrated success in multiple malignancies, yet their efficacy in ovarian cancer has been limited. Monotherapy with ICIs yields low response rates, prompting extensive investigations into combination strategies with chemotherapy, PARP inhibitors, and antiangiogenic agents. Some dual or triple regimens have shown promising activity, especially in biomarker-selected populations. However, immune resistance, immunosuppressive tumor microenvironment (TME), and biomarker heterogeneity remain significant barriers. This review summarizes the latest clinical progress in ICI-based therapies for ovarian cancer, evaluates current predictive biomarkers such as PD-L1 expression, TMB, and homologous recombination deficiency (HRD), and highlights the safety and toxicity profiles of immunotherapy. We also discuss the limitations of current clinical trials and the unmet need for precise immunotherapeutic strategies. Understanding the molecular and immunologic landscape of ovarian cancer is critical for identifying patients most likely to benefit from ICIs and guiding future clinical development.