PD-L1 deletion on T cells results in a pro-tumorigenic environment

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Presentation Time: 10:45 AM - 11:00 AM
Abstract ID: 5464 - B

Presenting Author:
Konstantinos Aliazis , Postdoctoral Research Fellow at Beth Israel Deaconess Med. Ctr., Harvard Med. Sch.

Abstract:

PD-L1 expressed in cancer and APC is an inhibitor of anti-tumor immunity by engaging PD-1 in T cells. PD-L1 is also expressed on activated T cells but its role in anti-tumor immunity is poorly understood. We generated mice with conditional targeting of the PD-L1 gene and crossed them with CD4Cre or LckCre mice to selectively delete PD-L1 in T cells. In vitro stimulation of splenic T cells showed that PD-L1 deletion enhanced activation of CD8+ T cells. To examine anti-tumor responses, we used the MC38 model. Similarly to in vitro stimulation, PD-L1 ablation resulted in enhanced activation of CD8+ but not CD4+ T cells.  To further investigate the effect of CD8-specific PD-L1 ablation in anti-tumor responses, we generated PD-L1 deficient mice expressing OTI, the CD8-specific transgenic TCR recognizing the OVA_257-264 peptide, and adoptively transferred OTI and PD-L1/OTI tumor antigen-specific T cells to CD45.1+ hosts bearing B16-Ova melanoma. Strikingly, recipients of PD-L1/OTI T cells had significantly larger tumors than recipients of OTI T cells, despite increased infiltration of TCR-transgenic CD8+ T cells with upregulation of CD69 and Ki67. These findings correlated with higher expression of PD-L1 on TAMs, M-MDSC, and PMN-MDSC. Our results indicate that PD-L1 ablation on CD8+ T cells confers an activated phenotype which leads to the generation of immunosuppressive myeloid cells in the TME and may be involved in adaptive immune resistance during checkpoint immunotherapy.