Unmasking T Cell Heterogeneity via Single Cell Transcriptomic Profiling

AACR 2018 -- Cancer immunotherapies that target regulatory pathways in T cells have led to important clinical advances in oncological treatments over the past decades. Checkpoint blockade therapies can lead to remarkable clinical responses. Clinical efficacy of various checkpoint inhibitors depends upon their ability to harness cytotoxic activity of T cells. Although cytotoxic ability of T lymphocytes (CTLs) are mostly the feature of conventional CD8+ T lymphocytes, the cytotoxic potential of TH cells (CD4-CTLs) in humans, nonhuman primates and mice has been reported for many decades. CD4-CTLs have been shown to elicit protective antitumor immune responses, especially in virally induced tumor. Understanding the mechanisms and pathways of the unique transcriptional state of CD4+ CTLs will help develop better strategies to develop immunotherapies. Given the importance of CD4-CTLs in immunotherapy and acquired cellular immunity, we present here unbiased approaches to evaluate cellular states and subpopulations of human CD4+ T cells, important aspects that may be concealed by targeted approaches such as FACS sorting on cell-surface antigens, or bulk expression analysis.