TY - JOUR T1 - Gut microbiota modulate T cell trafficking into human colorectal cancer JF - Gut JO - Gut DO - 10.1136/gutjnl-2016-313498 SP - gutjnl-2016-313498 AU - Eleonora Cremonesi AU - Valeria Governa AU - Jesus Francisco Glaus Garzon AU - Valentina Mele AU - Francesca Amicarella AU - Manuele Giuseppe Muraro AU - Emanuele Trella AU - Virginie Galati-Fournier AU - Daniel Oertli AU - Silvio Raffael Däster AU - Raoul A Droeser AU - Benjamin Weixler AU - Martin Bolli AU - Raffaele Rosso AU - Ulrich Nitsche AU - Nina Khanna AU - Adrian Egli AU - Simone Keck AU - Julia Slotta-Huspenina AU - Luigi M Terracciano AU - Paul Zajac AU - Giulio Cesare Spagnoli AU - Serenella Eppenberger-Castori AU - Klaus-Peter Janssen AU - Lubor Borsig AU - Giandomenica Iezzi Y1 - 2018/02/06 UR - http://gut.bmj.com/content/early/2018/02/06/gutjnl-2016-313498.abstract N2 - Objective Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers.Design Expression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues. Chemokine receptor expression on TILs was evaluated by flow cytometry on cell suspensions from digested tissues. Chemokine production by CRC cells was evaluated in vitro and in vivo, on generation of intraperitoneal or intracecal tumour xenografts in immune-deficient mice. T cell trafficking was assessed on adoptive transfer of human TILs into tumour-bearing mice. Gut flora composition was analysed by 16SrRNA sequencing.Results CRC infiltration by distinct T cell subsets was associated with defined chemokine gene signatures, including CCL5, CXCL9 and CXCL10 for cytotoxic T lymphocytes and T-helper (Th)1 cells; CCL17, CCL22 and CXCL12 for Th1 and regulatory T cells; CXCL13 for follicular Th cells; and CCL20 and CCL17 for interleukin (IL)-17-producing Th cells. These chemokines were expressed by tumour cells on exposure to gut bacteria in vitro and in vivo. Their expression was significantly higher in intracecal than in intraperitoneal xenografts and was dramatically reduced by antibiotic treatment of tumour-bearing mice. In clinical samples, abundance of defined bacteria correlated with high chemokine expression, enhanced T cell infiltration and improved survival.Conclusions Gut microbiota stimulate chemokine production by CRC cells, thus favouring recruitment of beneficial T cells into tumour tissues. ER -