Abstract
In the past 20 years, the immune system has increasingly been recognized as a major player in tumor cell control, leading to considerable advances in cancer treatment. While promising with regards to melanoma, renal cancer and non-small cell lung cancer, immunotherapy provides, for the time being, limited success in other cancers, including ovarian cancer, potentially due to insufficient immunogenicity or to a particularly immunosuppressive microenvironment. In this review, we provide a global description of the immune context of ovarian cancer, in particular epithelial ovarian cancer (EOC). We describe the adaptive and innate components involved in the EOC immune response, including infiltrating tumor-specific T lymphocytes, B lymphocytes, and natural killer and myeloid cells. In addition, we highlight the rationale behind the use of EOC preclinical mouse models to assess resistance to immunotherapy, and we summarize the main preclinical studies that yielded anti-EOC immunotherapeutic strategies. Finally, we focus on major published or ongoing immunotherapy clinical trials concerning EOC.
Highlights
Ovarian cancer is the most lethal among gynecological malignancies, due to diagnosis at advanced stages of the disease and to intrinsic and acquired resistance to chemotherapy in a large proportion of patients
Since the introduction of paclitaxel inro first-line treatment, no dramatic advances have been attained in epithelial ovarian cancers (EOC) patient progression-free survival, eliciting high expectations in new therapeutic strategies, such as immunotherapy
Recent and increasing evidence demonstrates that EOC tumors are infiltrated by cytotoxic T lymphocytes, key actors of the antitumor immune response and predictors of patient outcome
Summary
Ovarian cancer is the most lethal among gynecological malignancies, due to diagnosis at advanced stages of the disease and to intrinsic and acquired resistance to chemotherapy in a large proportion of patients. Progress has been made in the treatment of ovarian cancer by more aggressive surgical approaches and the introduction of platinum-taxane regimens, the 5-year overall survival for the advanced disease is approximately 30% [1]. The most frequent subtype, high-grade serous carcinoma (HGSC), accounts for approximately 80% of epithelial ovarian cancers (EOC). Therapies that harness and enhance antitumor effector cells, such as immune checkpoint blockade (ICB), have led to clinical benefits for several malignancies, including melanoma, non-small cell lung cancer and renal cell carcinoma [9]. The tight relationship between preexisting antitumor immune responses and patient responses to ICB in many cancer types [10] suggests that EOC patients may benefit from immunotherapy approaches. We will present an overview of clinical trials designed to assess the potential benefit of immune intervention in the treatment of EOC patients
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