THE ANALYSIS OF CD8+ T CELL ANTI-TUMOR RESPONSES

Immunotherapy treatments have been a growing trend for treatment cancer since 2012 with the first clinical trial for check point blockade therapy to treat melanoma patients. As researchers have studied the mechanism of action for immune directed killing of patients’ tumors, it is becoming clear how much we need to understand the biology of anti-tumor T cell responses to find the characteristics of a robust anti-tumor response. By studying the T cell receptor (TCR) repertoire of the endogenous tumor response in mice and patients, we have created a tool called ImmunoMap to measure and compare a T cell response by its TCR repertoire overtime and even between entirely different T cell targets, while previously only individual clonotypes or clones could be tracked. Along with ability to analyze T cell response both in research and clinical responses, our work have revealed that neo-antigen T cell response comparatively has benefits over self-tumor responses which explains the benefit of targeting patient’s cancers based on neo-antigen responses. But not all neo-antigen response show immunogenic response to tumors, which lead us to study a model of immunogenic neo-antigen response by antigen mimicry between commensal bacteria and a non-self tumor antigen. We are excited to show a proof-of-concept in murine melanoma of antigen mimicry in the gut led to a boosting of the tumor T cell response and colonization change and prime the T cell response to create a therapeutic T cell population. I am pleased with the work I have contributed in the Schneck lab, to study what effects the quality of an anti-tumor T cell responses and further understand ways to increase positive patient outcomes with immunotherapy treatments against cancer