RT Journal Article
SR Electronic
T1 Gut microbiota modulate T cell trafficking into human colorectal cancer
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1984
OP 1994
DO 10.1136/gutjnl-2016-313498
VO 67
IS 11
A1 Cremonesi, Eleonora
A1 Governa, Valeria
A1 Garzon, Jesus Francisco Glaus
A1 Mele, Valentina
A1 Amicarella, Francesca
A1 Muraro, Manuele Giuseppe
A1 Trella, Emanuele
A1 Galati-Fournier, Virginie
A1 Oertli, Daniel
A1 Däster, Silvio Raffael
A1 Droeser, Raoul A
A1 Weixler, Benjamin
A1 Bolli, Martin
A1 Rosso, Raffaele
A1 Nitsche, Ulrich
A1 Khanna, Nina
A1 Egli, Adrian
A1 Keck, Simone
A1 Slotta-Huspenina, Julia
A1 Terracciano, Luigi M
A1 Zajac, Paul
A1 Spagnoli, Giulio Cesare
A1 Eppenberger-Castori, Serenella
A1 Janssen, Klaus-Peter
A1 Borsig, Lubor
A1 Iezzi, Giandomenica
YR 2018
UL http://gut.bmj.com/content/67/11/1984.abstract
AB 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.