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Graft‐versus‐host disease reduces regulatory T ‐cell migration into the tumour tissue
Author(s) -
Dürr Christoph,
Follo Marie,
Idzko Marco,
Reichardt Wilfried,
Zeiser Robert
Publication year - 2012
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2012.03610.x
Subject(s) - immune system , haematopoiesis , inflammation , chemokine , t cell , biology , transplantation , immunology , cancer research , graft versus host disease , cell , cytotoxic t cell , stem cell , microbiology and biotechnology , medicine , in vitro , genetics , biochemistry
Summary The therapeutic principle of allogeneic haematopoietic cell transplantation (allo‐ HCT ) is based on an active donor immune system that eliminates host‐derived tumour cells. We hypothesized that in addition to the alloantigen‐driven anti‐tumour response, disruption of the immunological microenvironment within the tumour is responsible for its elimination after allo‐ HCT . We observed that induction of graft‐versus‐host disease ( GvHD ) significantly reduced the abundance of luc + F ox P 3 + regulatory T ( T reg) cells in the tumour tissue, which is indicative of impaired or over‐ridden tumour recruitment signals towards T reg cells. Analysis of the intestines and liver revealed chemokines and purine nucleotides as candidates for attracting T reg to these sites of inflammation. Despite its expression on tissue‐residing T reg cells, the chemokine receptor CCR 3 was not critical for T reg‐cell function following allo‐ HCT . Extracellular ATP can attract immune cells via P 2 Y 2. P 2 Y 2 was found to be expressed on T reg cells, and we found a partial reduction of GvHD prevention when P 2 Y 2 −/− rather than P 2 Y 2 +/+ Treg cells were given. Exogenous local inflammation reduced T reg‐cell accumulation in the tumour, suggesting a potential clinical approach to prevent T reg‐cell‐mediated tumour escape. In conclusion, we demonstrate that GvHD ‐related inflammation reduced Treg‐cell numbers at the tumour sites, which may in turn help to explain the observation that patients with GvHD have a lower risk of tumour relapse.