Entrance of activated T cells into the
tumor after adoptive transfer is a prerequisite for the efficacy of this form of
immunotherapy. Because lymphocyte binding to vascular endothelium is the critical step in which lymphocyte extravasation into the tissue is controlled, we compared adhesion of tumor-infiltrating lymphocytes (TIL) to endothelial cells in
tumors, peripheral lymph nodes, mucosa-associated lymphatic tissues, and inflamed synovium. Simultaneously, expression of the known homing-associated Ags both on TIL and
tumor vasculature was analyzed. All TIL strongly expressed alpha 4-integrins,
LFA-1 and CD44, whereas only a low level of
L-selectin expression was detected.
Tumor vasculature showed signs of activation in each patient on the basis of elevated levels of
intercellular adhesion molecule-1,
E-selectin,
vascular cell adhesion molecule-1, and/or
peripheral lymph node addressin (PNAd). TIL showed significantly enhanced binding to
tumor vasculature in comparison with other endothelial specificities. Increased binding was not markedly due to up-regulation of the
inflammation-induced endothelial cell adhesion molecules in
tumors, because binding to inflamed synovium that expressed the same adhesion molecules was not enhanced. In summary, TIL show preferential binding to
tumor vasculature and the binding is partially mediated by currently unknown mechanisms. In vitro analysis of endothelial cell binding properties may help to identify those TIL populations that will have the best potential to home back to
tumor tissue after adoptive transfer.