Liangliang Ji, PhD, Postdoctoral Fellow Memorial Sloan Kettering Cancer Center Cytotoxic T lymphocytes (CTLs) lose their cancer cell killing activities during tumor progression. Cancer immunotherapy including immune checkpoint blockade (ICB) aims to revive CTL responses, and has become a new paradigm to treat multiple types of cancer. Despite breakthrough success of ICB therapy, many patients do not benefit from it even among cancer indications considered to have the highest response rate. The limited efficacy of ICB calls for exploration of regulatory mechanisms of CTL dysfunction that may be a target for novel cancer immunotherapy. Tumor-associated macrophages (TAMs) are one of the most abundant immune cells in the tumor microenvironment. High infiltration of TAMs correlates with poor prognosis and impaired patient survival in various types of cancer. Dr. Ji’s preliminary data have demonstrated that TAMs with a specific gene program promote CTL dysfunction in murine and human malignancies. Dr. Ji will focus on investigating how TAMs acquire such a unique gene expression pattern in the tumor microenvironment, and how TAMs promote the differentiation of dysfunctional CTLs. Completion of this study will help the development of novel strategies for cancer immunotherapy. Projects and Grants Antigen-presenting cell control of CD8+ T cell exhaustion in cancer Memorial Sloan Kettering Cancer Center | All Cancers | 2022 | Ming Li, Ph.D.