Functional expression of beta1 and beta2 integrins on tumor infiltrating lymphocytes (TILs) in colorectal cancer.
Integrins play an important role in various lymphocyte functions. In this study, tumor-infiltrating lymphocytes (TIL) were isolated from colorectal cancer tissues and the expression of beta1 and beta2 integrins on the TIL was quantitatively examined with two-color flow cytometry. In comparison with peripheral blood lymphocytes (PBL), TIL expressed a lower level of common beta1 chain (CD29) in both CD4 and CD8 subpopulations. Among the associated alpha chains, the expressions of alpha1 (CD49a) and alpha2 (CD49b) were slightly higher in TIL than in PBL, whereas alpha4 (CD49d) and alpha6 (CD49f) were markedly downregulated in TIL. Both alphaL (CD11a) and beta2 (CD18) were reduced in CD8(+) TIL but not in CD4(+) TIL. TIL with the CD8(+) cytotoxic phenotype showed significantly decreased binding to purified intracellular adhesion molecules (ICAM)-1, and vascular adhesion cell molecule (VCAM)-1, and HT29 colon cancer cells, compared with the in counterparts in PBL. The peculiar expression pattern and functional down regulation of these integrins may explain why TIL in colorectal cancer cannot eradicate the malignant cells.
Kitayama
J
J
Department of Surgery, The University of Tokyo, Japan.
Nagawa
H
H
Nakayama
H
H
Tuno
N
N
Shibata
Y
Y
Muto
T
T
D000368:Aged; D018821:CD18 Antigens / Q000032:analysis*; D015704:CD4 Antigens / Q000032:analysis* / Q000096:biosynthesis; D016827:CD8 Antigens / Q000032:analysis* / Q000096:biosynthesis; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019012:Integrin beta1 / Q000032:analysis* / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D018821:CD18 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D019012:Integrin beta1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1