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.

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ObjectiveWhile human papillomavirus (HPV) infection in women is associated with cervical intraepithelial neoplasia and cervical cancer, HPV testing is not often performed in routine practice for renal transplantation patients. The genotype-specific prevalence of HPV and risk factors for HPV infection are still unclear.MethodsFrom 2010 to 2020, patients receiving renal transplantation surgery (referred to as RTRs), who had been screened for HPV infection one year after transplantation were enrolled. A comparison cohort of four age- and marital status-matched healthy individuals was selected for RTRs. The clinical characteristics and cervical screening results of RTRs were analyzed.ResultsOur study included 196 female renal transplant recipients (RTRs), none of whom had been vaccinated against HPV. Overall high-risk HPV (hrHPV) infection and abnormal cytology rates in the RTR group were 23.5% and 20.9%, respectively. The odds ratios of hrHPV infection and cervical intraepithelial neoplasia grade 2+ in RTRs vs. non-RTRs were 3.033 (95% CI, 2.013-4.568) and 3.628 (95% CI, 1.863-7.067), respectively. The prevalence of HPV16 in RTRs was much higher (30.4% vs. 8.3%, P=0.002). The multi-infection rate was much higher in HPV-infected RTRs (23.9% vs. 1.14%, P<0.001). The only risk factor for hrHPV infection was the duration of immunosuppression, which increased with time.ConclusionRTRs had significantly higher HPV infection rates and increased risks of HPV-related cervical premalignancies and cancers due to the immunosuppressed state. The duration of immunosuppression is a risk factor for transplant recipients. Female RTRs may benefit from more frequent cervical cancer screening after renal transplantation than healthy women. Prospective research on HPV infection dynamics in RTRs and optimal screening methods should be further explored in the future.