The Shanker laboratory studies information processing and signal transduction circuitry underlying lymphocyte crosstalk in response to physiological and pathological conditions. Our pioneering studies in the tumor microenvironment of murine solid tumors that express cancer-germline model antigen P1A discovered a new paradigm of CD8 T cell help for innate effector function. We showed that CD8+T cells provide necessary “help” to elicit natural killer (NK) cell antitumor function that potentiates immunosurveillance against tumor development and antigen escape (J Immunol 2007; Immunology 2010; J Transl Med 2013). Our ongoing work has identified mitochondrial Ca2+ transport-dependent intermembranous exchange and Notch–NFkB signaling crosstalk as key mechanisms guiding CD8+T–NK interaction to elicit NK cell effector/regulatory and T cell memory phenotypes (Open Biology 2016; Aging 2017). These findings provide novel immunotherapy approaches that can be developed to prevent tumor development and escape. Using the breast, kidney and inducible EGFR-mutant lung cancer mouse models, and patient samples in a multi-institutional team, we are testing various adoptive transfer protocols of CD8+T and NK cells in combination with immunomodulatory agents such as engineered Notch ligand clusters, bortezomib, a proteasome inhibitor, and neurotransmitter agonists (JNCI, 2008: Cancer Res, 2011; Cancer Res 2015; Oncotarget 2015; Oncotarget, 2017; JITC 2019). Dr. Shanker has published over 60 peer-reviewed studies and delivered over 70 invited talks on his work. His laboratory has provided a vibrant learning environment for over 45 undergraduate, doctoral, postdoctoral and medical trainees, who received multiple Meharry / Vanderbilt institutional as well as nationally-competitive awards from the AAI, AACR, SITC, ASCB and HHMI.