Abstract B188: CMTM6, beyond a regulator of PD-L1 expression

Expression of PD-L1 by tumor cells and by infiltrating immune cells represents a critical feature of cancer immune evasion. In line with this, clinical targeting of the PD-1 – PD-L1 axis forms one of the most significant breakthroughs in cancer treatment of the past years. To study the mechanisms that regulate PD-L1 expression, we have previously performed a FACS-based genetic screen and identified CMTM6, a functionally-uncharacterized protein, as a novel regulator of PD-L1 protein levels. Furthermore, we observed that CMTM6 forms a molecular complex with PD-L1 and enhances the ability of PD-L1-expressing tumor cells to inhibit T-cells. However, apart from this important role for CMTM6 in PD-L1 regulation, our understanding of this protein remains highly limited. To further characterize CMTM6, we surveyed its expression in major tissues and organs in the human body. Analysis by IHC and flow cytometry shows thaT-cells in immune-privileged tissues and in primary and secondary lymphoid organs express CMTM6. In addition, we explored other biologic roles of CMTM6. We found CMTM6 positively regulates and co-immunoprecipitates with the co-stimulatory molecule CD58. Taken together, these findings indicate a broader role for CMTM6 in immune modulation. Citation Format: Chong Sun*, Riccardo Mezzadra*, Raquel Gomez-Eerland*, Ingrid Hofland, Dennis Peters, Annegien Broeks, Hugo M. Horlings, Wei Wu, Albert J. R. Heck, Ton N.M. Schumacher. CMTM6, beyond a regulator of PD-L1 expression [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B188.