Journal
GENES & DEVELOPMENT
Volume 25, Issue 24, Pages 2559-2572Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.169029.111
Keywords
leukocyte; inflammation; chemotherapy; radiation therapy; cytotoxic therapy; cancer
Categories
Funding
- American Board of Radiology (ABR)
- Conquer Cancer Foundation of the American Society for Clinical Oncology (ASCO)
- Cancer Research UK
- Breast Cancer Research Foundation
- NIH/NCI
- Department of Defense [W81XWH-11-1-0702, PR080717]
- Susan G. Komen for the Cure Foundation [KG111084]
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Leukocytes and their soluble mediators play important regulatory roles in all aspects of solid tumor development. While immunotherapeutic strategies have conceptually held clinical promise, with the exception of a small percentage of patients, they have failed to demonstrate effective, consistent, and durable anti-cancer responses. Several subtypes of leukocytes that commonly infiltrate solid tumors harbor immunosuppressive activity and undoubtedly restrict the effectiveness of these strategies. Several of these same immune cells also foster tumor development by expression of potent protumor mediators. Given recent evidence revealing that immune-based mechanisms regulate the response to conventional cytotoxic therapy, it seems reasonable to speculate that tumor progression could be effectively diminished by combining cytotoxic strategies with therapies that blunt protumor immune-based effectors and/or neutralize those that instead impede development of desired anti-tumor immunity, thus providing synergistic effects between traditional cytotoxic and immune-modulatory approaches.
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