Immunosuppression in Ovarian Cancer and the Path to Successful Immunotherapy
A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".
Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 20805
Special Issue Editor
Special Issue Information
Ovarian cancer has the fifth highest mortality rate among women diagnosed with cancer in Europe. Ovarian cancer is a silent killer, metastasizing throughout the abdomen before causing any symptoms. Consequently, 63% of patients are detected at FIGO stage III or IV, leading to an overall 5-year survival of only 20%. The introduction of maximal cytoreductive debulking surgery, Bevacizumab (anti-VEGF (vascular endothelial growth factor)) and PARP inhibitors (Poly (ADP-ribose) polymerase) have drastically improved survival, but with a relapse rate of still 80%, we face certain boundaries.
The immune system is now known to play a pivotal role in the onset and development of cancer. The adaptive and innate immune responses are mobilized to eliminate neoplastic cells as they emerge. In some cases, elimination is not entirely successful and an equilibrium phase is established, whereby neoplastic cells enter a dormant state, side by side with the immune system. During this process, tumor cells can be edited and consequently escape this immunological control. Eventually, the immune system fails and uncontrolled tumor proliferation occurs. Tumors themselves and/or through their interaction with the microenvironment may attract immunosuppressive cells, such as MDSC (myeloid derived suppressor cells), Treg (regulatory T cells), tumor promoting M2 macrophages, and others, to divert immune detection and facilitate unregulated tumor growth. Immunological evasion arises in all tumors, but the key players establishing the immune suppressive microenvironment are different per tumor, maybe even for different stages of the disease. Knowledge of the immune system in ovarian cancer is, so far, mainly limited to the intratumoral behavior of the adaptive immune system. The success rate of immune checkpoint inhibitor therapy in monotherapy is 10% for ovarian cancer. This is far below the success rate in, for example, melanoma (45% with Nivolumab). Because of the highly aggressive nature of ovarian cancer, this is hardly a surprise. Combinatorial strategies, combining immunotherapy with, for example, chemotherapy, are mandatory. However, the first results of these combinatorial trials have been disappointing as well. The JAVELIN Ovarian 100 and 200 trials were prematurely stopped because the primary endpoints (increase of survival) were not reached. In the JAVELIN Ovarian 100, the combinations had a reduced survival compared to chemotherapy alone (Figure 1). Additionally, in 2008, Alberts et al. published a study combining carboplatin-paclitaxel with interferon gamma 1 beta, which resulted in a decreased survival compared to chemotherapy alone.
Understanding and dealing with the specific immune biology of ovarian cancer is a mandatory key to successful immunotherapy. Therefore, we believe it is necessary to group all relevant information on this topic to increase the power of immunotherapeutic strategies in ovarian cancer.
Prof. Dr. An Coosemans
Guest Editor
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Keywords
- immunosuppression
- ovarian cancer
- immunotherapy
- MDSC
- Treg
- macrophages
- neutrophils
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