Back to Search
Start Over
Differentiation and Regulation of TH Cells: A Balancing Act for Cancer Immunotherapy
- Source :
- Frontiers in Immunology, Vol 12 (2021), Frontiers in Immunology
- Publication Year :
- 2021
- Publisher :
- Frontiers Media S.A., 2021.
-
Abstract
- Current success of immunotherapy in cancer has drawn attention to the subsets of TH 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 TH subsets in the tumor milieu further contributes to the complexity of regulation of TH cell-mediated immune response. In this review, we present an overview of the multifaceted positive and negative effects of TH cells, with an emphasis on regulation of different TH 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+ 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 Tfh cells, immunosuppressive Treg cells, and the duality of TH17 function contribute to tip the balance of anti- vs pro-tumorigenic TH responses 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 TH cell subtypes can be explored further to amplify immunotherapy success in patients. Understanding the nuances of CD4+ TH cells regulation and the molecular framework undergirding the balancing act between anti- vs pro-tumorigenic TH subtypes is critical for rational designing of immunotherapies that can bypass therapeutic escape to maximize the potential of immunotherapy.
- Subjects :
- Cytotoxicity, Immunologic
0301 basic medicine
medicine.medical_treatment
Immunology
Cell
Priming (immunology)
Review
Lymphocyte Activation
Cancer Vaccines
Immunotherapy, Adoptive
03 medical and health sciences
Lymphocytes, Tumor-Infiltrating
0302 clinical medicine
Immune system
Cancer immunotherapy
Antigens, Neoplasm
Neoplasms
T helper
Tumor Microenvironment
Animals
Humans
Immunology and Allergy
Medicine
Cytotoxic T cell
business.industry
Cancer
Cell Differentiation
T-Lymphocytes, Helper-Inducer
Immunotherapy
RC581-607
medicine.disease
CD4
neoantigen
Phenotype
030104 developmental biology
medicine.anatomical_structure
Cancer research
Cytokines
tumor associated antigen
immunotherapy
Immunologic diseases. Allergy
business
CD8
Signal Transduction
T-Lymphocytes, Cytotoxic
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....4857d1f416262432de7701d26c641680