Advancing Cancer Immunotherapy: An Intimate Play of CD8 T and NK Cells



25 - October -2017    Duration: 14:30 PM To 15:30 PM

Venue: Seminar Hall, Main Building

A special seminar by Dr. Anil Shankar, Associate Professor of Biochemistry and Cancer Biology & Member, Vanderbilt-Ingram Cancer Center and Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University, USA. He did PhD in Biotechnology (Tumor Immunology) from Banaras Hindu University, India in 1999. Click here to know more about to Dr. Anil Shankar

 

Abstract:

The central theme of Shanker laboratory is to develop strategies that can empower cytolytic function of lymphocytes in the battle against cancer and its relapse. In models of solid tumors, our pioneering studies uncovered a new paradigm of adaptive control of innate antitumor immunity. We found that tumor-infiltrating CD8 T lymphocytes provide an indispensable “help” to natural killer (NK) cells in eliciting their antitumor effector function, which leads to complete regression of tumors including their escape variants. We identified intracellular mitochondrial Ca2+ transport and Notch–NFkBcrosstalk as key signaling controllers guiding CD8 T–NK interaction and cellular remodeling underlying NK cell effector/regulatory and T cell memory phenotypes.Working with breast, kidney and inducible EGFR-mutant lung cancer mouse models, and patient samples in a multi-institutional collaborative team, our findings provide new avenues to prevent tumor escape and metastasis by overcoming lymphocyte suppression in the tumor microenvironment. This work has led to new translational efforts that we have initiated for enhancing the potential of immunotherapy following adoptive transfers of CD8 T and NK cells in combination with immunomodulatory agents such as bortezomib, a proteasome inhibitor, multivalent Notch ligand clusters, and neurotransmitters.