Video On Demand: Kinetics of tumor cell killing by tumor-infiltrating lymphocytes

Cara Haymaker, Ph.D, Assistant Professor, University of Texas MD Anderson Cancer Center

This presentation focuses on utilization of the ACEA xCELLigence system to assess the kinetics of tumor-infiltrating lymphocyte (TIL) recognition and killing of autologous or HLA-matched primary tumor cell lines. The classical methods of assessing tumor killing by an effector T cells relies upon an estimation of the timing of this recognition and as such, this event may be missed. MDACC has a robust program utilizing autologous transfer of TIL (TIL ACT) for the treatment of metastatic melanoma as well as other solid tumors. One avenue of research within the team is to expand TIL from solid tumors as well as establish an autologous tumor line to assess reactivity of the TIL. This provides an opportunity to modulate mechanisms of resistance to therapy and explore biomarkers of response. One major example was the identification of B-and-T lymphocyte attenuator (BTLA) as an inhibitory molecule that also marks less-differentiated serial killing CD8+ TIL. In addition, we are exploring means to make TIL resistant to suppression mediated by TGFbeta signaling through the use of a dominant negative TGFbeta receptor. Overall the xCELLigence system allows for a non-biased timing approach to explore the impact of TIL modification on their ability to kill HLA-matched or autologous tumor cells.

 

 

Cara Haymaker, Ph.D
Assistant Professor
University of Texas MD Anderson Cancer Center

I am an Assistant Professor in the Department of Translational Molecular Pathology at MDACC. My lab is focused on assessing ways to modulate intratumoral APCs to improve antigen presentation and costimulation to TIL, thus improving response to cellular and antibody based immunotherapies in solid tumors. In addition, I am heavily involved in the immune monitoring of clinical trials performed at MDACC through both the Translational Molecular Pathology-Immunoprofiling lab (TMP-IL, operational director) and the Oncology Research and Immune-monitoring core (ORION, Director).