Colon cancer is a leading cause of morbidity and death in Americans. There is increasing evidence that bacterially-induced inflammation increases risk of intestinal cancer. We have recently developed a novel lymphocyte-deficient mouse model of microbially induced carcinoma that resembles colon cancer in humans. The invasive colon cancer that develops in this mouse model is treatable using CD4+CD25+ regulatory lymphocytes. We propose to use this rapidly inducible cancer platform of colitis-associated cancer to investigate how CD4+CD25+ regulatory cells are able to treat colon cancer. We have also recently found that CD4+CD25+ cells induce regression of intestinal tumors in the ApcMin/+ mouse model of colorectal cancer. We propose to apply this widely used cancer platform to investigate how CD4+CD25+ are able to treat colorectal cancer not so clearly linked with intestinal inflammation. We speculate that regulatory cells work by delivering IL10 to down-modulate inflammation that sustains cancer.
We aim to probe inflammatory and neoplastic events to identify targets to disrupt neoplastic invasion. Information gained from these studies may elucidate pivotal mechanisms and uncover novel strategies for prevention and treatment of human colon cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Cancer Immunopathology and Immunotherapy Study Section (CII)
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Daschner, Phillip J
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Massachusetts Institute of Technology
Veterinary Sciences
Other Domestic Higher Education
United States
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Erdman, Susan E; Poutahidis, Theofilos (2017) Gut microbiota modulate host immune cells in cancer development and growth. Free Radic Biol Med 105:28-34
Varian, Bernard J; Poutahidis, Theofilos; DiBenedictis, Brett T et al. (2017) Microbial lysate upregulates host oxytocin. Brain Behav Immun 61:36-49
Poutahidis, Theofilos; Erdman, Susan E (2016) Commensal bacteria modulate the tumor microenvironment. Cancer Lett 380:356-8
Poutahidis, Theofilos; Varian, Bernard J; Levkovich, Tatiana et al. (2015) Dietary microbes modulate transgenerational cancer risk. Cancer Res 75:1197-204
Doulberis, Michael; Angelopoulou, Katerina; Kaldrymidou, Eleni et al. (2015) Cholera-toxin suppresses carcinogenesis in a mouse model of inflammation-driven sporadic colon cancer. Carcinogenesis 36:280-90
Erdman, Susan E; Poutahidis, Theofilos (2015) Gut bacteria and cancer. Biochim Biophys Acta 1856:86-90
Levkovich, Tatiana; Poutahidis, Theofilos; Cappelle, Kelsey et al. (2014) 'Hygienic' lymphocytes convey increased cancer risk. J Anal Oncol 3:113-121
Erdman, S E; Poutahidis, T (2014) Probiotic 'glow of health': it's more than skin deep. Benef Microbes 5:109-19
Poutahidis, Theofilos; Springer, Alex; Levkovich, Tatiana et al. (2014) Probiotic microbes sustain youthful serum testosterone levels and testicular size in aging mice. PLoS One 9:e84877
Lakritz, Jessica R; Poutahidis, Theofilos; Levkovich, Tatiana et al. (2014) Beneficial bacteria stimulate host immune cells to counteract dietary and genetic predisposition to mammary cancer in mice. Int J Cancer 135:529-40

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