The role of vascular cell adhesion molecule-1 in tumor immune evasion

Abstract

Tumor immune escape is a critical trait of cancer but the mechanisms involved have yet to fully emerge. One recent study has shown that tumor cells can escape T-cell immunity by overexpressing the endothelial cell adhesion molecule vascular cell adhesion molecule-1 (VCAM-1), which normally mediates leukocyte extravasion to sites of tissue inflammation. Renal cell carcinoma (RCC) was identified as one tumor type where VCAM-1 is commonly highly overexpressed. Together, our findings suggest that RCCs might exploit VCAM-1 overexpression for immune escape.

Figure 1

Model for VCAM-1–mediated tumor immune evasion. A model is proposed for the role on VCAM-1 in tumor immune evasion. A, in the case of VCAM-1–expressing tumor cells, VCAM-1 on the tumor cell binds to α₄β₁ integrin, the receptor for VCAM-1 on the surface of the T cells. This interaction leads to migration of the T cells away from the tumor and decreased infiltration of T cells into the tumor, thus leading to tumor immune evasion. B, in the case of tumor cells not expressing VCAM-1, there is no interaction with α₄β₁ integrin on the T cells. The tumor cells present the tumor antigen through MHC class I molecule to the T-cell receptor on the CD8⁺ T cell, thus activating the T cells and leading to increased infiltration of the T cells into the tumor. This results in tumor killing (X).