The past decade of tumor immunology has taught us that most tumors express targets for T cells and many elicit experimentally detectable T cell responses.  Many factors limit the tumor-recognizing T cells from killing tumors; tumors and the resident inflammatory cells have numerous ways of inhibiting productive T cells responses.  In addition, most T cells recognize antigens on tumors that are “self antigens” not “neoantigens” or mutated proteins that lead to tumor development.  Therefore T cells bind weakly to tumor and, rather than vigorously responding to the tumor, they make half-hearted responses.  Poor T cell responses to self antigens seem detrimental, but actually this protects us from other autoimmune issues.  If T cells could be better stimulated when encountering tumors, they might mediate more effective responses against the tumor.  Our goal is to make this happen.

 

Part of the lab is determining what amino acid substitutions in tumor antigens improve antitumor immunity.  These so-called “mimotope” peptides (mimics of epitopes) activate T cells that respond to the tumor more effectively than the natural tumor antigen.  To understand how mimotope peptides affect T cell responses against tumors, we are characterizing the T cells responding to these peptides.  We are also determining the contribution of autoimmune responses to tumors using animals in which the tumor antigen is a “self antigen,” compared to animals in which the tumor antigen is a “foreign antigen.”  Success of these studies will have direct implications for the design and development of tumor vaccines.