‘Hygienic’ Lymphocytes Convey Increased Cancer Risk

Risk of developing inflammation-associated cancers has increased in industrialized countries during the past 30 years. One possible explanation is societal hygiene practices with use of antibiotics and Caesarian births that provide too few early life exposures of beneficial microbes. Building upon a...

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Bibliographic Details
Main Authors: Levkovich, Tatiana, Poutahidis, Theofilos, Cappelle, Kelsey, Smith, Mark Burnham, Perrotta, Allison Rose, Alm, Eric J., Erdman, Susan E.
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: Lifescience Global 2015
Online Access:http://hdl.handle.net/1721.1/99236
https://orcid.org/0000-0001-8294-9364
https://orcid.org/0000-0003-4700-5987
https://orcid.org/0000-0003-4378-9542
Description
Summary:Risk of developing inflammation-associated cancers has increased in industrialized countries during the past 30 years. One possible explanation is societal hygiene practices with use of antibiotics and Caesarian births that provide too few early life exposures of beneficial microbes. Building upon a ‘hygiene hypothesis’ model whereby prior microbial exposures lead to beneficial changes in CD4+ lymphocytes, here we use an adoptive cell transfer model and find that too few prior microbe exposures alternatively result in increased inflammation-associated cancer growth in susceptible recipient mice. Specifically, purified CD4+ lymphocytes collected from ‘restricted flora’ donors increases multiplicity and features of malignancy in intestinal polyps of recipient Apc[superscript Min/+] mice, coincident with increased inflammatory cell infiltrates and instability of the intestinal microbiota. We conclude that while a competent immune system serves to maintain intestinal homeostasis and good health, under hygienic rearing conditions CD4+ lymphocytes instead exacerbate inflammation-associated tumorigenesis, subsequently contributing to more frequent cancers in industrialized societies.