Description:

Title: 

Role of TIM Family of Genes in Regulating Anti-Tumor Immunity

Speaker:

Vijay Kuchroo, Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston

Topic: 

T cell Immunoglobulin and Mucin containing molecules 3 (Tim-3), first identified as a molecule expressed on IFN-g producing T cells, is emerging as an important immune-checkpoint molecule whose therapeutic blockade is currently being investigated in multiple human malignancies. While expression of Tim-3 on CD8+ T cells in the tumor microenvironment is considered a cardinal sign of terminal T cell dysfunction, Tim-3 is also expressed on several other immune cells, confounding the interpretation of immunological and clinical results following blockade using anti-Tim-3 monoclonal antibodies.  Using conditional knockouts of Tim-3 together with single-cell RNA-seq, we demonstrate the singular importance of Tim-3 expression in dendritic cells (DCs), whereby loss of Tim-3 on DCs, promotes strong anti-tumor immunity by regulating Inflammasome activation. Another family member Tim-1 has been found to be expressed on a subset of B cells that expand during tumor growth. Selective deletion of Havcr1 (the gene encoding TIM-1) in B cells both dramatically inhibited tumor growth and enhanced effector T cell responses.  Our results demonstrate that besides T cells, TIM -family of proteins may be checkpoint molecules on other cell types as well and manipulation of the Tim-3 and Tim-1 enables the engagement of DCs and B cells to promote anti-tumor immunity and inhibit tumor growth.”

Host:

Pablo Penaloza-MacMaster, PhD, Assistant Professor, Dept. Of Microbiology-Immunology