Abstract
Ovarian cancer (OvCA) accounts for one of the leading causes of death from gynecologic malignancy. Despite progress in therapy improvements in OvCA, most patients develop a recurrence after first-line treatments, dependent on the tumor and non-tumor complexity/heterogeneity of the neoplasm and its surrounding tumor microenvironment (TME). The TME has gained greater attention in the design of specific therapies within the new era of immunotherapy. It is now clear that the immune contexture in OvCA, here referred as tumor immune microenvironment (TIME), acts as a crucial orchestrator of OvCA progression, thus representing a necessary target for combined therapies. Currently, several advancements of antitumor immune responses in OvCA are based on the characterization of tumor-infiltrating lymphocytes, which have been shown to correlate with a significantly improved clinical outcome. Here, we reviewed the literature on selected TIME components of OvCA, such as macrophages, neutrophils, γδ T lymphocytes, and natural killer (NK) cells; these cells can have a role in either supporting or limiting OvCA, depending on the TIME stimuli. We also reviewed and discussed the major (immune)-therapeutic approaches currently employed to target and/or potentiate macrophages, neutrophils, γδ T lymphocytes, and NK cells in the OvCA context.
Highlights
Ovarian cancer (OvCA) is one of the most common gynecologic malignancies [1], and it is characterized by relatively high incidence, poor prognosis, and a very high mortality rate [2]
Surgery is effective in most cases of early stage (FIGO stages I–IIA) with a 5-year survival rate of around 90%, but more than 70% of patients are diagnosed with advanced disease (FIGO stages III–IV) presenting malignant ascites which is an indicator of poor prognosis
The OvCA tumor microenvironment (TME) displays unique features leading to immune suppression and tolerance; this impairs both the presence and the activity of immune system components including tumor-associated macrophages (TAMs), neutrophils, γδ T cells, and natural killer (NK) cells
Summary
Ovarian cancer (OvCA) is one of the most common gynecologic malignancies [1], and it is characterized by relatively high incidence, poor prognosis, and a very high mortality rate [2]. After the “genomic era”, a relevant shift to the host cells as target, first with endothelial cells and angiogenesis and recently with impaired immune response as a principal hallmark of many tumors, occurred This knowledge has launched numerous clinical trials testing immunotherapy, starting with melanoma, lung, colon cancer and OvCA [20]. Several cells of both innate and adaptive immunity, including tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs), γδ T cells, and natural killer (NK) cells, directly or indirectly (via soluble interactions) shape the peritoneal TME, creating a permissive environment for tumor development and a favorable metastatic soil [18,19]. We discuss on macrophages, neutrophils, γδ T cells, and NK cells as relevant TIME-drivers in OvCA progression and as targets for immune therapy
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