Journal
CANCER IMMUNOLOGY RESEARCH
Volume 2, Issue 10, Pages 1011-1022Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-13-0207
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Funding
- RSNA Research and Education Research Resident Grant
- American Cancer Society [RSG-12-168-01-LIB]
- M.J. Murdoch Charitable Trust
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The immune infiltrate in colorectal cancer has been correlated with outcome, such that individuals with higher infiltrations of T cells have increased survival independent of the disease stage. For patients with lower immune infiltrates, overall survival is limited. Because the patients with colorectal cancer studied have received conventional cancer therapies, these data may indicate that the pretreatment tumor environment increases the efficacy of treatments such as chemotherapy, surgery, and radiotherapy. This study was designed to test the hypothesis that an improved immune environment in the tumor at the time of treatment will increase the efficacy of radiotherapy. Wedemonstrate that inhibition of TGF beta using the orally available small-molecule inhibitor SM16 improved the immune environment of tumors in mice and significantly improved the efficacy of subsequent radiotherapy. This effect was not due to changes in radiosensitivity, epithelial-mesenchymal transition, or changes in vascular function in the tumor; rather, this effect was dependent on adaptive immunity and resulted in long-term protective immunity in cured mice. These data demonstrate that immunotherapy is an option to improve the immune status of patients with poor tumor infiltrates and that pretreatment improves the efficacy of radiotherapy. (C) 2014 AACR.
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