| First Author | Schiering C | Year | 2010 |
| Journal | Cancer Res | Volume | 70 |
| Issue | 15 | Pages | 6161-70 |
| PubMed ID | 20631073 | Mgi Jnum | J:162232 |
| Mgi Id | MGI:4818497 | Doi | 10.1158/0008-5472.CAN-09-4398 |
| Citation | Schiering C, et al. (2010) Antigen-Experienced CD4+ T Cells Limit Naive T-Cell Priming in Response to Therapeutic Vaccination In vivo. Cancer Res 70(15):6161-70 |
| abstractText | CD4(+) T cells play a central role in protective immunity. In a mouse tumor model, we previously found that tumor growth elicits natural CD4(+) T-cell responses, but impedes therapeutic vaccination. We show here that inhibition of vaccine-mediated naive T-cell priming is due to the presence of a minor but distinct population of tumor-reactive CD4(+) T cells. These cells are generated in the tumor draining lymph nodes (LN), are capable of systemic redistribution, and act to limit the representation of antigen-bearing MHC II(+) antigen-presenting cells (APC) in contralateral LNs or when transferred to tumor-free mice. Surgical tumor resection, which lowers the representation of tumor primed CD4(+) T cells, restored to some extent vaccine-induced CD4(+) T-cell activation. Likewise, vaccination with artificial APCs (latex beads) or higher numbers of dendritic cells allowed comparable CD4(+) T-cell priming in tumor-free and tumor-bearing mice. Together, our results emphasize the ability of antigen-experienced CD4(+) T lymphocytes to interfere with therapeutic vaccination and highlight the need for alternative strategies able to surmount limitations imposed by ongoing immune responses. Cancer Res; 70(15); 6161-70. (c)2010 AACR. |
