The Central Role of CD4+ T Cells in the Antitumor Immune Response

Hung, Kenneth; Hayashi, Robert; Lafond-Walker, Anne; Lowenstein, Charles; Pardoll, Drew; Levitsky, Hyam

doi:10.1084/jem.188.12.2357

Cited by 1,345Immunotherapy and Immune ResponsesT-cell and B-cell ImmunologyCancer Immunotherapy and Biomarkers

The Central Role of CD4+ T Cells in the Antitumor Immune Response

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Hung, Kenneth, Hayashi, Robert, Lafond-Walker, Anne, Lowenstein, Charles, Pardoll, Drew, Levitsky, Hyam·1998·The Journal of Experimental Medicine

DOI 10.1084/jem.188.12.2357PMC PMC2212434

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Abstract

The induction of optimal systemic antitumor immunity involves the priming of both CD4+ and CD8+ T cells specific for tumor-associated antigens. The role of CD4+ T helper cells (Th) in this response has been largely attributed to providing regulatory signals required for the priming of major histocompatibility complex class I restricted CD8+ cytolytic T lymphocytes, which are thought to serve as the dominant effector cell mediating tumor killing. However, analysis of the effector phase of tumor rejection induced by vaccination with irradiated tumor cells transduced to secrete granulocyte/macrophage colony-stimulating factor indicates a far broader role for CD4+ T cells in orchestrating the host response to tumor. This form of immunization leads to the simultaneous induction of Th1 and Th2 responses, both of which are required for maximal systemic antitumor immunity. Cytokines produced by these CD4+ T cells activate eosinophils as well as macrophages that produce both superoxide and nitric oxide. Both of these cell types then collaborate within the site of tumor challenge to cause its destruction.

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Tumor rejection that depends on CD4+ Th cells and NK cells but not on CD8+ T cell activity has been observed.
“However, tumor rejection that depends on CD4+ Th cells and NK cells but not on CD8+ T cell activity has been observed213–215.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [215]

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Authors: Hung, K., Hayashi, R., Lafond-Walker, A., Lowenstein, C., Pardoll, D., & Levitsky, H.
Affiliations: Johns Hopkins University (US)
Corresponding author: Levitsky, Hyam
ORCID: Hung, Kenneth
Hayashi, Robert
Lowenstein, Charles
Pardoll, Drew
Levitsky, Hyam
Venue: The Journal of Experimental Medicine
Publisher: Rockefeller University Press
Published: 1998-12-21
Volume: 188
Issue: 12
Pages: 2357-2368
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.188.12.2357
PMC: PMC2212434
OpenAlex: W2138733343
Cited by: 1,345
References: 99
Citations by year: 2026: 10 · 2025: 24 · 2024: 25 · 2023: 30 · 2022: 29 · 2021: 40 · 2020: 37 · 2019: 31 · 2018: 30 · 2017: 34 · 2016: 30 · 2015: 48 · 2014: 42 · 2013: 45 · 2012: 43
FWCI: 21.84
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Experimental Medicine (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Funders: Johns Hopkins University
National Institute of Allergy and Infectious Diseases (AI/AG37934-01)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords: CD4+ T cells, antitumor immunity, T helper cells, CD8+ cytotoxic T lymphocytes, tumor-associated antigens, Th1/Th2 immune response, GM-CSF, eosinophils, macrophages, nitric oxide, superoxide, tumor rejection
MeSH terms: Animals, Cell Movement, Cytotoxicity, Immunologic, Eosinophils, Female, T-Lymphocytes, Helper-Inducer, Injections, Subcutaneous, Lymphocyte Cooperation, Macrophages, Melanoma, Experimental, Mice, Inbred C57BL, Antigens, CD, Granulocyte-Macrophage Colony-Stimulating Factor, Cytokines, Mice, Knockout, CD8-Positive T-Lymphocytes, Nitric Oxide Synthase, NADPH Oxidases, Cancer Vaccines, Mice, Nitric Oxide Synthase Type II

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The Central Role of CD4+ T Cells in the Antitumor Immune Response

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