CD4 T-cell immunotherapy for chronic viral infections and cancer

• Type of Material: Article
• Authors: Alice O Kamphorst Silva, Emory University; Rafi Ahmed, Emory University
• Language: English
• Date: 2013-09
• Publisher: Future Medicine
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Future Medicine Ltd
• Final Published Version (URL): http://www.futuremedicine.com/doi/abs/10.2217/imt.13.91?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed
• Title of Journal or Parent Work: Immunotherapy
• ISSN: 1750-743X
• Volume: 5
• Issue: 9
• Grant/Funding Information: This work was supported by grants from the NIH R01 AI030048 and P01 A1080192 (R Ahmed) and by the Irvington Institute Fellowship Program of the Cancer Research Institute (AO Kamphorst).
• Keywords: immunotherapy; cancer; CD4 T cells; chronic infection; exhaustion; PD-1; adoptive cell transfer
• Research Categories: Health Sciences, Immunology; Health Sciences, Oncology; Biology, Microbiology

Abstract

During chronic infections and cancer, T cells progressively lose function and become exhausted. However, effective T-cell responses are necessary to ultimately control viral infections and tumors. Hence, strategies that either restore endogenous immune responses or provide functional T cells by adoptive immunotherapy need to be explored. CD8 T cells play a prominent role in viral infections, as well as cancer, but CD4 T cells are necessary to support CD8 T-cell function. In addition, CD4 T cells exert direct effector functions, induce optimal B-cell responses and orchestrate innate immunity. Therefore, we propose that adoptive transfer strategies should exploit CD4 T cells alone or in combination with CD8 T cells, for the treatment of chronic infections and cancer. Furthermore, since adoptively transferred cells are subject to exhaustion, combining adoptive transfer therapy with immunotherapies that inhibit T-cell exhaustion should maximize the longevity and success rate of responses.