The Interplay Between Regular T Cells and Immunotherapy in Cervical Cancer
Background: Immune checkpoint blockade inhibitors have aroused great expectation on many types of tumor eradication. However, the therapeutic effect of anti-PD-L1 treatment on cervical cancer is unsatisfactory and the potential antagonist is not very clear. Here, we investigated the therapeutic effect of anti-PD-L1 in cervical tumor mouse model and identified the potential threats for anti-PD-L1 therapeutic efficacy.
Results: we found that PD-L1 had a moderate expression in human and mouse cervical tumor cell lines and clinical samples compared to other tumor types and para-tumor tissue. Interestingly, our results showed that the anti-PD-L1 treated mice were dichotomously divided into responsive and unresponsive group even with the same genome background C57BL/6 syngeneic tumor model. The unresponsive tumors showed less immune cell infiltration and higher Tregs population induced immunosuppression activity than the responsive ones. Furthermore, we found that anti-PD-L1 autonomously upregulated Tregs proliferation and frequency in multiple immune organs, and, most importantly, Tregs depletion more significantly depressed the tumor growth rate and tumor weight than either anti-PD-L1 or anti-CD25 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.
Conclusion: In conclusion, anti-PD-L1 therapy upregulates Tregs frequency and proliferation in tumor model, and the depletion of Tregs may be a useful adjuvant strategy for anti-PD-L1 therapy in the immunotherapy of cervical cancer.
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Posted 30 Dec, 2020
Invitations sent on 01 Jan, 2021
On 01 Jan, 2021
On 28 Dec, 2020
On 28 Dec, 2020
On 19 Dec, 2020
The Interplay Between Regular T Cells and Immunotherapy in Cervical Cancer
Posted 30 Dec, 2020
Invitations sent on 01 Jan, 2021
On 01 Jan, 2021
On 28 Dec, 2020
On 28 Dec, 2020
On 19 Dec, 2020
Background: Immune checkpoint blockade inhibitors have aroused great expectation on many types of tumor eradication. However, the therapeutic effect of anti-PD-L1 treatment on cervical cancer is unsatisfactory and the potential antagonist is not very clear. Here, we investigated the therapeutic effect of anti-PD-L1 in cervical tumor mouse model and identified the potential threats for anti-PD-L1 therapeutic efficacy.
Results: we found that PD-L1 had a moderate expression in human and mouse cervical tumor cell lines and clinical samples compared to other tumor types and para-tumor tissue. Interestingly, our results showed that the anti-PD-L1 treated mice were dichotomously divided into responsive and unresponsive group even with the same genome background C57BL/6 syngeneic tumor model. The unresponsive tumors showed less immune cell infiltration and higher Tregs population induced immunosuppression activity than the responsive ones. Furthermore, we found that anti-PD-L1 autonomously upregulated Tregs proliferation and frequency in multiple immune organs, and, most importantly, Tregs depletion more significantly depressed the tumor growth rate and tumor weight than either anti-PD-L1 or anti-CD25 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.
Conclusion: In conclusion, anti-PD-L1 therapy upregulates Tregs frequency and proliferation in tumor model, and the depletion of Tregs may be a useful adjuvant strategy for anti-PD-L1 therapy in the immunotherapy of cervical cancer.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF.