Work

CD40 stimulation accelerates deletion of tumor-specific CD8 + T cells in the absence of tumor-antigen vaccination

Year: 2001

Type: article

Abstract: Previous work has established a role for CD40-mediated signals in eliciting helper-dependent CD8(+) T cell responses. Here we investigated the effects of in vivo CD40 stimulation on the survival and function of tumor-specific CD8(+) T cells in a mouse melanoma model system. We found that agonistic anti-CD40 antibody treatment alone of tumor-bearing mice accelerated the deletion of tumor-antigen-specific T cells. However, long-term survival and function of tumor-antigen-specific T cells could be achieved when viral immunization with tumor antigen and anti-CD40 treatment were combined. This rescue of CD8(+) T cells could not be easily replicated by inflammatory or antigen-specific stimuli alone, demonstrating the specificity of signals that regulate the deletion or survival of tumor-specific T cells. These results demonstrate that opposing effects can be elicited by CD40 stimulation in vivo and suggest the need for caution in using this treatment for cancer patients.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.191371898

Authors: Ross M. Kedl, Michael Jordan, Terence Potter, John Kappler, Philippa Marrack, Steven Dow

Institutions: Howard Hughes Medical Institute, National Jewish Health, University of Colorado Cancer Center

Language: English

Topic: Immunotherapy and Immune Responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Cancer Research Institute, U.S. Public Health Service, National Cancer Institute, National Institute of Allergy and Infectious Diseases