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

Area of Science:

• Gynecologic Oncology
• Immunotherapy
• Cancer Research

Background:

• Ovarian cancer is a lethal malignancy with high recurrence and poor prognosis, especially in platinum-resistant cases.
• Immune checkpoint inhibitors (ICIs) have limited efficacy as monotherapy in ovarian cancer, despite success in other cancers.
• The immunosuppressive tumor microenvironment (TME) and biomarker heterogeneity present significant barriers to ICI treatment.

Purpose of the Study:

• To review the clinical progress of ICI-based therapies in ovarian cancer.
• To evaluate predictive biomarkers for ICI efficacy, including PD-L1 expression, tumor mutational burden (TMB), and homologous recombination deficiency (HRD).
• To discuss the safety, toxicity, limitations of current trials, and unmet needs in ovarian cancer immunotherapy.

Main Methods:

• Literature review of clinical trials and research on ICI-based therapies for ovarian cancer.
• Analysis of current predictive biomarkers (PD-L1, TMB, HRD) and their role in patient selection.
• Evaluation of safety and toxicity profiles of immunotherapies in ovarian cancer patients.

Main Results:

• Monotherapy with ICIs has low response rates in ovarian cancer.
• Combination strategies (chemotherapy, PARP inhibitors, antiangiogenic agents) show promising activity, particularly in biomarker-selected populations.
• Immune resistance and TME factors limit ICI effectiveness.

Conclusions:

• Understanding the molecular and immunologic landscape of ovarian cancer is crucial for improving ICI efficacy.
• Precise immunotherapeutic strategies are needed to overcome resistance and identify patients likely to benefit from ICIs.
• Further research and optimized clinical trials are essential for advancing ovarian cancer immunotherapy.