Adenosine suppresses α4β7 integrin-mediated adhesion of T lymphocytes to colon adenocarcinoma cells

Willena M. MacKenzie, David W. Hoskin, Jonathan Blay

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

The interaction of T lymphocytes with tumor cells, a key step in the antitumor immune response, is suppressed by adenosine, a nucleoside produced at increased levels within the hypoxic tumor environment. We have explored the mechanism by which adenosine interferes with the lymphocyte:tumor cell interaction. The adhesion of anti-CD3-stimulated T cells to syngeneic MCA-38 mouse colon adenocarcinoma cells did not involve LFA-1 (αLβ2) or VLA-5 (α5β1). However, antibodies against either lymphocyte α4 or β7 (but not β1) integrin subunits, or against VCAM-1 on the tumor cells, significantly suppressed adhesion, showing that the recognition of MCA-38 cells by T cells is strongly dependent upon the association of α4β7 on the effector cells with VCAM-1 on the tumor targets. This association is modulated by adenosine: The ability of adenosine to suppress T cell adhesion to MCA-38 cells was lost if α4β7 was functionally blocked with anti-α4 antibodies (i) prior to or (ii) during the adhesion assay or if (iii) α4+ cells were depleted from the T lymphocyte population. The binding of T cells to fibronectin through α4β1 was not suppressed by adenosine. We conclude that adenosine partially inhibits the interaction of T lymphocytes with tumor cells by blocking the function of integrin α4β7.

Original languageEnglish
Pages (from-to)90-100
Number of pages11
JournalExperimental Cell Research
Volume276
Issue number1
DOIs
Publication statusPublished - 2002

Bibliographical note

Funding Information:
1 This work was supported by grants to J.B. and D.W.H. from the Natural Sciences and Engineering Research Council (NSERC) of Canada and by a Ciba-Geigy/MRC studentship to W.M.M.

ASJC Scopus Subject Areas

  • Cell Biology

PubMed: MeSH publication types

  • Journal Article

Fingerprint

Dive into the research topics of 'Adenosine suppresses α4β7 integrin-mediated adhesion of T lymphocytes to colon adenocarcinoma cells'. Together they form a unique fingerprint.

Cite this