Efficacy of cancer immunotherapy with cultured tumour-infiltrating lymphocytes (TILs) depends upon infused TILs migrating into tumour-bearing tissue, in which they mediate an anti-tumour response. For TILs to enter a tumour, they must first bind to tumour endothelium, and this process depends on TILs expressing and regulating the function of relevant cell-surface receptors. We analysed the cell-surface phenotype and endothelial binding of TILs cultured from human melanoma and compared them with peripheral blood T cells and with allostimulated T cells cultured under similar conditions. Compared with peripheral blood T cells, TILs expressed high levels of five integrins, two other adhesion molecules, including the skin homing molecule CLA, and several activation markers and showed markedly enhanced integrin-mediated adhesion to a dermal microvascular endothelial cell line in vitro. Compared with the allostimulated T cells, TILs expressed higher levels of the cutaneous lymphocyte antigen (CLA), the adhesion molecule CD31 and the activation markers CD30 and CD69, but lower levels of several other adhesion and activation molecules. These phenotypic and functional properties of TILs should have complex effects on their migration in vivo. Expression of CLA, the skin homing receptor, may increase migration to melanoma (a skin cancer), whereas integrin activation may cause non-specific binding of TILs to other endothelium. Manipulation of the culture conditions in which TILs are expanded might result in a phenotype that is more conducive to selective tumour homing in vivo.
|Number of pages
|British Journal of Cancer
|Published - 1997
Bibliographical noteFunding Information:
We thank the staff of the Clinical Immunotherapy Laboratory, Surgery Branch, NCI, for their help in preparing TIL samples; Liana Harvath for help with the confocal microscopy of actin staining; Yoshiya Tanaka and Tamas Schweighoffer for helpful advice; Dr Louis Picker for critical review of the manuscript; many generous colleagues for providing MAb; G Ginther-Luce and N Graber for technical assistance; our volunteer blood donors and the NIH Blood Bank. DHA was supported by the Eli Lilly/Medical Research Council 1991/1992 Travelling Fellowship and the Fogarty Exchange Program.
- Tumour-infiltrating lymphocytes
ASJC Scopus subject areas
- Cancer Research