High-Dimensional Profiling of Tumor-Specific Immune Responses: Asking T Cells about What They “See” in Cancer

Abstract The foundations of basic T-cell immunology and an understanding of the roles for T cells in controlling cancer have led to the remarkable yet inconsistent success of cancer immunotherapy. Because of these advances in cancer treatment, the need is urgent for biomarkers that can predict the efficacy of these treatments and for new therapeutic strategies for cases where currently available approaches are ineffective. Although our ability to profile heterogeneous cell populations in human blood or tissue samples has vastly improved in the past decade, identifying the cell subsets relevant to diseases, and to cancer particularly, remains a challenge. Given strong evidence for the implication of T cells specific for tumor-expressed antigens in various forms of effective immunotherapy, here, we focus on the utility, challenges, and techniques for the identification and profiling of these important cells. We review recent techniques that allow identifying and profiling of tumor-specific T cells. As these methods improve, we can expect more rapid progress in the rational design of novel cancer biomarkers and therapies based on antigen-specific T cells. Cancer Immunol Res; 6(1); 2–9. ©2018 AACR.