Immunotherapies have revolutionized the treatment of a variety of cancers. Epithelial ovarian cancer is the most lethal gynecologic malignancy, and the rate of advanced tumor progression or recurrence is as high as 80%. Current salvage strategies for patients with recurrent ovarian cancer are rarely curative. Recurrent ovarian cancer is a “cold tumor”, predominantly due to a lack of tumor antigens and an immunosuppressive tumor microenvironment. In trials testing programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) blockade as a monotherapy, the response rate was only 8.0-22.2%. In this review, we illustrate the status of cold tumors in ovarian cancer and summarize the existing clinical trials investigating PD-1/PD-L1 blockade in recurrent ovarian cancer. Increasing numbers of immunotherapy combination trials have been set up to improve the response rate of EOC. The current preclinical and clinical development of immunotherapy combination therapy to convert an immune cold tumor into a hot tumor and their underlying mechanisms are also reviewed. The combination of anti-PD-1/PD-L1 with other immunomodulatory drugs or therapies, such as chemotherapy, antiangiogenic therapies, poly (ADP-ribose) polymerase inhibitors, adoptive cell therapy, and oncolytic therapy, could be beneficial. Further efforts are merited to transfer these results to a broader clinical application.

Although high-grade serous cancer (HGSC) accounts for >70% of ovarian epithelial cancers, it is rarely associated with endometriosis. No previous study has reported an association between the malignant transformation of uterine ligament endometriosis and HGSC. Here, we reported two cases of Chinese female patients with HGSC arising from endometriosis in the uterosacral ligament. They had a long-term history of endometriosis and dysmenorrhea. Both were diagnosed with HGSC at stage IIB. They underwent operations and six cycles of chemotherapy with paclitaxel and carboplatin and have remained disease-free to date. Genomic analysis showed no known/suspected pathogenic variations or somatic homologous recombination deficiency in the two cases. In conclusion, these rare cases of HGSC from endometriosis might indicate a new origin of ovarian type II carcinoma. Patients with a long-term history of endometriosis and sudden aggravation of dysmenorrhea or vaginal bleeding should be aware of the possibility of endometriotic malignant transformation.