Abstract
BackgroundImmune checkpoint inhibitors have aroused great expectation of tumor eradication. However, the effect of anti-PD-L1 treatment for cervical cancer is unsatisfactory and the underlying antagonist to anti-PD-L1 efficacy is remained to be studied. Here, we investigated the anti-tumor effect of anti-PD-L1 treatment in cervical tumor model and identified the antagonist to the therapeutic efficacy of anti-PD-L1 treatment.ResultsWe found that PD-L1 exhibited a moderate expression in both cervical tumor cell lines and clinical samples compared to other tumor types and the para-tumor tissue respectively. Interestingly, our results showed that the anti-PD-L1 treated mice were dichotomously divided into responsive and unresponsive group after five cycles of anti-PD-L1 treatment although all the mice had the same genome background. In addition, the unresponsive tumors showed less tumor necrosis area and higher immunosuppression activity induced by regulatory T cells (Tregs) population than the responsive ones. Furthermore, we found that anti-PD-L1 treatment autonomously upregulated Tregs proliferation and frequency in multiple immune organs, and, most importantly, Tregs depletion significantly depressed the tumor growth rate and tumor weight compared with either anti-PD-L1 or anti-CD25 treatment alone. Finally, we observed that the upregulating effector CD8+ T cell is associated with the better therapeutic effect of anti-PD-L1 therapy post Tregs depletion.ConclusionsAnti-PD-L1 treatment upregulates Tregs frequency and proliferation in tumor model, and the depletion of Tregs may be a useful adjuvant strategy for anti-PD-L1 therapy of cervical cancer.
Highlights
Cervical cancer, as the second most malignant gynecological tumor with high incidence and high mortality among women, severely threats women’s health all around the world [1, 2]
The initiation and progression of cervical cancer are associated with the immunosuppression on C D4+ and CD8+ T cells caused by human papillomavirus (HPV) infection
Previous studies showed that tumoral PD-L1 expression was observed in 72% cervical and vulvar squamous carcinomas (SCC) and 95% cervical intraepithelial neoplasias (CINs) [9, 12]
Summary
As the second most malignant gynecological tumor with high incidence and high mortality among women, severely threats women’s health all around the world [1, 2]. Immune checkpoint inhibitors, such as PD-1, PD-L1 and CTLA4, have been intensely studied in many solid tumors, and many clinical trials have shown the long-lasting improved prognosis of patients, especially in melanoma and lung cancer [8,9,10]. As for cervical cancer, antiCTLA-4 showed little clinical efficacy in patients with recurrence or metastasis [11]. Meng et al reported that 61% (59/97) of the patients exhibited PD-1 expression in the tumor stroma of cervical cancer [13]. The therapeutic efficiency of anti-PD-L1 treatment is urgent to be improved in advanced cervical cancer. The effect of anti-PD-L1 treatment for cervical cancer is unsatisfactory and the underlying antagonist to anti-PD-L1 efficacy is remained to be studied. We investigated the anti-tumor effect of anti-PD-L1 treatment in cervical tumor model and identified the antagonist to the therapeutic efficacy of anti-PD-L1 treatment
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
