Differentiation and Regulation of TH Cells: A Balancing Act for Cancer Immunotherapy
Abstract
Current success of immunotherapy in cancer has drawn attention to the subsets of THcells 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 THsubsets in the tumor milieu further contributes to the complexity of regulation of THcell-mediated immune response. In this review, we present an overview of the multifaceted positive and negative effects of THcells, with an emphasis on regulation of different THcell 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+TH1 cells and subsequent priming of CD8+cytotoxic T cells, along with intersecting anti-inflammatory and pro-tumorigenic TH2 cell activity. We further discuss how other tumor infiltrating immune cells such as immunostimulatory TH9 and Tfhcells, immunosuppressive Tregcells, and the duality of TH17 function contribute to tip the balance of anti- vs pro-tumorigenic THresponses in the tumor. We highlight the developing knowledge of CD4+TH1 immune response against neoantigens/oncodrivers, impact of current immunotherapy strategies on CD4+TH1 immunity, and how opposing action of THcell subtypes can be explored further to amplify immunotherapy success in patients. Understanding the nuances of CD4+THcells regulation and the molecular framework undergirding the balancing act between anti- vs pro-tumorigenic THsubtypes is critical for rational designing of immunotherapies that can bypass therapeutic escape to maximize the potential of immunotherapy.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 03, 2021
- Source ID
- 10.3389/fimmu.2021.669474
Entities
People
- Amber Beyer
- Amrita Basu
- Brian J. Czerniecki
- Colin Snyder
- Corey Gallen
- Gabriella Albert
- Ganesan Ramamoorthi
- Gary K. Koski
- Krithika Kodumudi
- Mary L. Disis
Organizations
- United States Department of Defense