Differentiation and Regulation of T H Cells: A Balancing Act for Cancer Immunotherapy

Current success of immunotherapy in cancer has drawn attention to the subsets of T cells in the tumor which are critical for activation of anti-tumor response either directly by themselves or by stimulating cytotoxic T cell activity. However, presence of immunosuppressive pro-tumorigenic T subsets i...

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Bibliographic Details
Published in:Frontiers in immunology 2021-05, Vol.12, p.669474
Main Authors: Basu, Amrita, Ramamoorthi, Ganesan, Albert, Gabriella, Gallen, Corey, Beyer, Amber, Snyder, Colin, Koski, Gary, Disis, Mary L, Czerniecki, Brian J, Kodumudi, Krithika
Format: Article
Language:English
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Summary:Current success of immunotherapy in cancer has drawn attention to the subsets of T cells in the tumor which are critical for activation of anti-tumor response either directly by themselves or by stimulating cytotoxic T cell activity. However, presence of immunosuppressive pro-tumorigenic T subsets in the tumor milieu further contributes to the complexity of regulation of T cell-mediated immune response. In this review, we present an overview of the multifaceted positive and negative effects of T cells, with an emphasis on regulation of different T cell subtypes by various immune cells, and how a delicate balance of contradictory signals can influence overall success of cancer immunotherapy. We focus on the regulatory network that encompasses dendritic cell-induced activation of CD4 T 1 cells and subsequent priming of CD8 cytotoxic T cells, along with intersecting anti-inflammatory and pro-tumorigenic T 2 cell activity. We further discuss how other tumor infiltrating immune cells such as immunostimulatory T 9 and T cells, immunosuppressive T cells, and the duality of T 17 function contribute to tip the balance of anti- vs pro-tumorigenic T responses in the tumor. We highlight the developing knowledge of CD4 T 1 immune response against neoantigens/oncodrivers, impact of current immunotherapy strategies on CD4 T 1 immunity, and how opposing action of T cell subtypes can be explored further to amplify immunotherapy success in patients. Understanding the nuances of CD4 T cells regulation and the molecular framework undergirding the balancing act between anti- vs pro-tumorigenic T subtypes is critical for rational designing of immunotherapies that can bypass therapeutic escape to maximize the potential of immunotherapy.
ISSN:1664-3224
DOI:10.3389/fimmu.2021.669474