T-cell mediated anti-tumor responses are critical for effective cancer immunotherapy. The ability of memory T cells to rapidly respond to antigens makes them key players in the protective immunity against cancer. Active immunization and memory T cell generation in vivo are regulated by both stimulatory and inhibitory factors. Although the presence of memory T cells proximal to tumors could be a good prognostic factor, they usually cannot control tumor progression because of dysfunction or tumor immune evasion. Restored function of memory T cells may also control the differentiation and proliferation of cancer stem cell to prevent cancer recurrence and metastasis. Our long term goal is to understand and manipulate the memory immune response to treat human cancers.

The process of T cell activation is mediated by: (a) antigen/MHC complex and the antigen-specific T cell receptor ; (b) positive or negative co-stimulatory molecules (B7s, B7-H1) and their receptors (CD28/CTLA-4, PD-1); (c) the cytokine- and chemokine-mediated signals that are required for T cell proliferation, migration, survival, and differentiation. Our research objectives are: (1)Define the molecular mechanisms that have negative impact on anti-tumor memory T cell generation and function; (2)Define the network of inter-cellular interactions critical for optimal tumor-specific T memory cell generation and function, including interactions among T cell subsets (Treg cells, T helper cells) and interactions of T cells with innate immune cells (NK, NKT, Macrophages); (3)Develop strategies to modify antigen presenting cells to promote tumor-specific memory T cell generation; (4)Identify the strategies to recognize and eliminate cancer stem cells by memory T cell immunity.