Vascular adhesion protein-1 and ICAM-1 support the adhesion of tumor-infiltrating lymphocytes to tumor endothelium in human hepatocellular carcinoma.
T cell-mediated mechanisms are important in the defense against solid organ tumors. Why some tumors are more heavily infiltrated by T cells than others is poorly understood but is likely to depend upon adhesive interactions between circulating lymphocytes and tumor endothelium. In support of this hypothesis, the present study shows that primary human hepatocellular carcinomas (HCC) are more heavily infiltrated with T cells than colorectal hepatic metastases (CHM), and that their tumor vessels express high levels of several adhesion molecules. In HCC, an intense T cell infiltrate is observed within the tumor associated with strong expression of ICAM-1 and vascular adhesion protein-1 (VAP-1) on tumor endothelium. In contrast, fewer T cells infiltrated CHM and these tumors have little ICAM-1 and no detectable VAP-1 or VCAM-1 on tumor endothelium. T cells infiltrating both tumors are LFA-1 and very late Ag (VLA)-4 high. In vitro tissue-binding studies demonstrated that T cells bound readily to tumor endothelium in HCC, and Abs to ICAM-1, VAP-1, and to a lesser extent VCAM-1 could inhibit this binding. VAP-1 supported sialic acid-dependent adhesion under shear stress, suggesting that VAP-1 and ICAM-1 mediate, respectively, tethering and firm adhesion. In contrast, very few T cells bound to tumor vessels in CHM. Thus our data suggest that the VAP-1/VAP-1 receptor and ICAM-1/LFA-1 pathways are important in the recruitment of T cells to HCC. The strong expression of VAP-1 on tumor endothelium distinguishes HCC from CHM and supports our previous hypothesis that VAP-1 is an important hepatic endothelial adhesion molecule.
Yoong
K F
KF
Liver Research Laboratories, Queen Elizabeth Hospital, Birmingham, United Kingdom.
McNab
G
G
Hübscher
S G
SG
Adams
D H
DH
D000328:Adult; D000368:Aged; D006631:Amine Oxidase (Copper-Containing); D000911:Antibodies, Monoclonal; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology; D004727:Endothelium / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)