Antitumor Activity Correlates With the Generation of Breast Tumor Specific Type 1 T Cells
Abstract
When vaccination fails to protect the host from a subsequent challenge with a tumor, that tumor is generally characterized as nonimmunogenic. This designation suggests that the host has not recognized, or is tolerant of the tumor antigens. Our recent studies suggest that this is not true. We have demonstrated that progressively growing subcutaneous tumors sensitize tumor-specific T cells; however, the antigen-reactive T cells are polarized to secrete type 2 (T2) cytokines (e.g. IL-4 and IL-l0), and lack therapeutic activity upon adoptive transfer. Conversely, immunogenic tumors induce predominantly type 1 (T1) antitumor responses, exhibiting highly polarized tumor-specific IFN-7 secretion. This proposal examines issues that are critical to understanding the mechanism for tumor regression following vaccination/immunotherapy. The first issue is whether tumor-specific T2 T cells, induced by progressively growing tumor, can inhibit the therapeutic efficacy of tumor-specific T1 T cells in our 4T1 mammary tumor model. If T2 T cells can inhibit therapeutic T cells it offers an explanation for the failure of tumor vaccine strategies and a possible approach to circumvent the inhibitory effect of T2 T cells. Aim 2 will test whether promoting a T1 response to vaccination will convert the nonimmunogenic 4T1 mammary tumor into a therapeutic vaccine
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADB262700
Entities
People
- Bernard Fox
Organizations
- Providence Portland Medical Center