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J. Li et al.
vation. However, sustained activation of T cells with anti- gen, IL-2 and IL-7 resulted in increased PVRIG expression by day 11.
This study reveals unique aspects of PVRIG biology that should be considered when determining potential indica- tions for its therapeutic use. Our results suggest that PVRIG blockade may still have a therapeutic effect, pro- vided the tumor cells express the PVRL2hiPVRlo pheno- type. Furthermore, when AML blasts express both PVRL2 and PVR, combination PVRIG and TIGIT blockade may also induce an effective NK-cell mediated anti-tumor response. These findings also have broader implications for the study of other checkpoint receptors. As more novel receptors are identified as potential targets, they should not be assumed to have the same biology as previously established immune checkpoints, and their potential effi-
cacy should not necessarily be measured by the same parameters.
Disclosures
No conflicts of interest to disclose.
Contributions
JL, DM and CD performed research, analyzed data and wrote the manuscript; SW, MK, KH, DM, KH, SL and JH provided academic input, shared key reagents, and wrote the manuscript; JAT and PJN supervised the project and wrote the manuscript.
Funding
Research funding for this project was provided by Compugen Inc. In the prior 36 months, PN also received research funding from BMS, Roche Genentech and Allergan.
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