Direct tumor recognition by a human CD4+ T-cell subset potently mediates tumor growth inhibition and orchestrates anti-tumor immune responses Journal Article
| Authors: | Matsuzaki, J.; Tsuji, T.; Luescher, I. F.; Shiku, H.; Mineno, J.; Okamoto, S.; Old, L. J.; Shrikant, P.; Gnjatic, S.; Odunsi, K. |
| Article Title: | Direct tumor recognition by a human CD4+ T-cell subset potently mediates tumor growth inhibition and orchestrates anti-tumor immune responses |
| Abstract: | Tumor antigen-specific CD4+ T cells generally orchestrate and regulate immune cells to provide immune surveillance against malignancy. However, activation of antigen-specific CD4+ T cells is restricted at local tumor sites where antigen-presenting cells (APCs) are frequently dysfunctional, which can cause rapid exhaustion of anti-tumor immune responses. Herein, we characterize anti-tumor effects of a unique human CD4+ helper T-cell subset that directly recognizes the cytoplasmic tumor antigen, NY-ESO-1, presented by MHC class II on cancer cells. Upon direct recognition of cancer cells, tumor-recognizing CD4+ T cells (TR-CD4) potently induced IFN-γ3-dependent growth arrest in cancer cells. In addition, direct recognition of cancer cells triggers TR-CD4 to provide help to NY-ESO-1-specific CD8+ T cells by enhancing cytotoxic activity, and improving viability and proliferation in the absence of APCs. Notably, the TR-CD4 either alone or in collaboration with CD8+ T cells significantly inhibited tumor growth in vivo in a xenograft model. Finally, retroviral gene-engineering with T cell receptor (TCR) derived from TR-CD4 produced large numbers of functional TR-CD4. These observations provide mechanistic insights into the role of TR-CD4 in tumor immunity, and suggest that approaches to utilize TR-CD4 will augment anti-tumor immune responses for durable therapeutic efficacy in cancer patients. |
| Journal Title: | Scientific Reports |
| Volume: | 5 |
| ISSN: | 2045-2322 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2015-10-08 |
| Start Page: | 14896 |
| Language: | English |
| DOI: | 10.1038/srep14896 |
| PROVIDER: | scopus |
| PMCID: | PMC4597193 |
| PUBMED: | 26447332 |
| DOI/URL: | |
| Notes: | Export Date: 2 November 2015 -- Source: Scopus |
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