4.7 Article

Cancer inflammation and regulatory T cells

Journal

INTERNATIONAL JOURNAL OF CANCER
Volume 127, Issue 4, Pages 768-779

Publisher

WILEY
DOI: 10.1002/ijc.25430

Keywords

gut bacteria; inflammation; T-REG cells; cancer

Categories

Funding

  1. NIH [R01CA108854]
  2. DOD [W81XWH-05-01-0460]
  3. Pythagoras II Grant [80860]

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Chronic inflammation is essential for cancer growth and metastasis. It follows that factors reducing inflammation would abrogate cancer and restore tissue health. However, roles for anti-inflammatory CD4+ regulatory cells (T-REG) in cancer are enigmatic and controversial. Our recent data reveal that T-REG may function in cancer similarly to inflammatory bowel disease or multiple sclerosis, whereby T-REG accumulate but lack potency to restore tissue homeostasis under inflammatory conditions. Interestingly, early life exposures to diverse environmental organisms reinforce a protective T-REG phenotype that inhibits cancer. In contrast, hygienic individuals with few exposures earlier in life suffer from a dysregulated T-REG feedback loop. Consequently, hygienic subjects have increased risk of malignancy later in life. This cancer condition is reversible by blocking underlying inflammation. Taken together, these data help explain increased inflammation-associated cancer rates in hygienic societies and identify targets to abrogate cancer and restore overall health.

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