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Research Article
The Interplay Between Regular T Cells and Immunotherapy in Cervical Cancer
Lihua Wang
Shanghai Jiao Tong University
Corresponding Author
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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.
Keywords
anti-PD-L1, Immune, T cells, Cancer
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CURRENT STATUS: Under Review
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This preprint is under consideration at BMC Immunology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
The Interplay Between Regular T Cells and Immunotherapy in Cervical Cancer
Lihua Wang
Shanghai Jiao Tong University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 30 Dec, 2020
No community comments so far
Reviewers invited
Invitations sent on 01 Jan, 2021
Editor assigned
On 01 Jan, 2021
Editor invited
On 28 Dec, 2020
Submission checks complete
On 28 Dec, 2020
First submitted
On 19 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Immunology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.