Qiao Lu, PhD, Postdoctoral Fellow New York University Medical Center As the self-derived “demon,” tumor cells can grow uncontrollably and actively suppress T cells, one of the key “guardians” that plays a critical role in combating tumors, by interacting with immune “brake” molecules expressed on the surface of T cells. Releasing the immune “brake” can restore the T cell activity against tumor cells and has shown great promise in clinical studies. However, many cancer patients do not respond to or develop resistance to the immunotherapies that help release the immune “brake.” One of the reasons for this is that “smart” tumor cells can avoid being recognized by T cells through “hiding” the “demon’s horn,” namely tumor antigens. Thus, it is necessary to understand how tumor cells can reduce the display or presentation of tumor antigens and identify those tumor-derived antigen presentation regulators. Using genetic methods, Dr. Lu has identified two cell surface proteins, Sushi domain-containing protein 6 (SUSD6) and Transmembrane protein 127 (TMEM127), that can potently suppress tumor antigen presentation. A robust increase in antigen presentation and significantly better control of tumor growth when either protein was depleted in tumor cells has been observed by Dr. Lu. In this proposal, he seeks to understand how both proteins regulate tumor antigen presentation and determine if it’s possible to develop novel cancer immunotherapies by targeting the two molecules. His proposed multidisciplinary and translational studies will not only advance our knowledge in cancer-associated regulation of antigen presentation pathways but also provide new candidates for next-generation cancer immunotherapy. Projects and Grants Tumor-associated evasion of antigen presentation as targets for next-generation cancer immunotherapy New York University Medical Center | All Cancers | 2022 | Jun Wang, Ph.D.