Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 May 4;9(5):454.
doi: 10.3390/vaccines9050454.

Impact of Immunotherapy on CD4 T Cell Phenotypes and Function in Cancer

Affiliations
Review

Impact of Immunotherapy on CD4 T Cell Phenotypes and Function in Cancer

Margaux Saillard et al. Vaccines (Basel). .

Abstract

Immunotherapy has become a standard treatment in many cancers and it is based on three main therapeutic axes: immune checkpoint blockade (ICB), vaccination and adoptive cell transfer (ACT). If originally these therapies mainly focused on exploiting CD8 T cells given their role in the direct elimination of tumor cells, increasing evidence highlights the crucial role CD4 T cells play in the antitumor immune response. Indeed, these cells can profoundly modulate the tumor microenvironment (TME) by secreting different types of cytokine or by directly eliminating cancer cells. In this review, we describe how different CD4 T cell subsets can contribute to tumor immune responses during immunotherapy and the novel high-throughput immune monitoring tools that are expected to facilitate the study of CD4 T cells, at antigen-specific and single cell level, thus accelerating bench-to-bed translational research in cancer.

Keywords: CD4 T cells; antigen-specific; cancer; immune monitoring; immunotherapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
CD4 T cell subsets and tumor immunity. Each CD4 T cell polarization can be defined by the secretion of cytokines and the presence of a master transcription factor. The polarization of CD4 T cells is influenced by the TME and is linked with either tumor-promoting (red) or -suppressive functions (green).
Figure 2
Figure 2
Summary of vaccination strategies and their impacts on CD4 T cell responses.
Figure 3
Figure 3
Summary of (DC)-based vaccinations for CD4 T cell activation.
Figure 4
Figure 4
Summary of ACT therapies exploiting CD4 T cells.

Similar articles

Cited by

References

    1. Fridman W.H., Zitvogel L., Sautes-Fridman C., Kroemer G. The immune contexture in cancer prognosis and treatment. Nat. Rev. Clin. Oncol. 2017;14:717–734. doi: 10.1038/nrclinonc.2017.101. - DOI - PubMed
    1. Tay R.E., Richardson E.K., Toh H.C. Revisiting the role of CD4(+) T cells in cancer immunotherapy-new insights into old paradigms. Cancer Gene Ther. 2020 doi: 10.1038/s41417-020-0183-x. - DOI - PMC - PubMed
    1. Haabeth O.A., Lorvik K.B., Yagita H., Bogen B., Corthay A. Interleukin-1 is required for cancer eradication mediated by tumor-specific Th1 cells. Oncoimmunology. 2016;5:e1039763. doi: 10.1080/2162402X.2015.1039763. - DOI - PMC - PubMed
    1. Laheurte C., Dosset M., Vernerey D., Boullerot L., Gaugler B., Gravelin E., Kaulek V., Jacquin M., Cuche L., Eberst G., et al. Distinct prognostic value of circulating anti-telomerase CD4(+) Th1 immunity and exhausted PD-1(+)/TIM-3(+) T cells in lung cancer. Br. J. Cancer. 2019;121:405–416. doi: 10.1038/s41416-019-0531-5. - DOI - PMC - PubMed
    1. Ling A., Lundberg I.V., Eklof V., Wikberg M.L., Oberg A., Edin S., Palmqvist R. The infiltration, and prognostic importance, of Th1 lymphocytes vary in molecular subgroups of colorectal cancer. J. Pathol. Clin. Res. 2016;2:21–31. doi: 10.1002/cjp2.31. - DOI - PMC - PubMed