Adenosine suppresses alpha(4)beta(7) integrin-mediated adhesion of T lymphocytes to colon adenocarcinoma cells.

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 (alpha(L)beta(2)) or VLA-5 (alpha(5)beta(1)). However, antibodies against either lymphocyte alpha(4) or beta(7) (but not beta(1)) 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 alpha(4)beta(7) 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 alpha(4)beta(7) was functionally blocked with anti-alpha(4) antibodies (i) prior to or (ii) during the adhesion assay or if (iii) alpha(+)(4) cells were depleted from the T lymphocyte population. The binding of T cells to fibronectin through alpha(4)beta(1) 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 alpha(4)beta(7).

• Authors: Willena M MacKenzie, David W Hoskin, Jonathan Blay
• Journal: Experimental cell research (Exp Cell Res) Vol. 276 Issue 1 Pg. 90-100 (May 15 2002) ISSN: 0014-4827 [Print] United States
• PMID: 11978011 (Publication Type: Journal Article)

Chemical References

• Antibodies
• Fibronectins
• Immunosuppressive Agents
• Integrin alpha4beta1
• Integrins
• Lymphocyte Function-Associated Antigen-1
• Receptors, Fibronectin
• Receptors, Lymphocyte Homing
• Vascular Cell Adhesion Molecule-1
• integrin alpha4beta7
• Adenosine

Topics

• Adenocarcinoma (immunology)
• Adenosine (pharmacology)
• Animals
• Antibodies (pharmacology)
• Cell Adhesion (drug effects)
• Cells, Cultured
• Colonic Neoplasms (immunology)
• Fibronectins (metabolism)
• Immunosuppressive Agents (pharmacology)
• Integrin alpha4beta1
• Integrins (antagonists & inhibitors, immunology, physiology)
• Lymphocyte Function-Associated Antigen-1 (physiology)
• Mice
• Mice, Inbred C57BL
• Receptors, Fibronectin (physiology)
• Receptors, Lymphocyte Homing (physiology)
• T-Lymphocytes (drug effects, immunology)
• Tumor Cells, Cultured
• Vascular Cell Adhesion Molecule-1 (immunology, metabolism)