Constitutive absence and interferon-gamma-induced expression of adhesion molecules in basal cell carcinoma.
Adhesion of lymphocytes to target cells via certain cell surface molecules is important in cytotoxic T lymphocyte-mediated immune reactions. The binding of lymphocyte function-associated (LFA) antigens 1 and 2, with their respective ligands, intercellular adhesion molecule-1 (ICAM-1) and LFA-3, which are expressed on the surface of nonlymphoid cells, has been shown to be critical for lymphocyte adhesion. To determine whether basal cell carcinomas (BCCs) can escape immunodetection as a result of the inability of cytotoxic T lymphocytes to bind tumor cells, the expression of adhesion molecules on numerous BCCs, before and after exposure to interferon-gamma (IFN-gamma), was examined. Ninety-three percent of 30 freshly excised invasive BCCs did not express ICAM-1 and 73% of 11 BCCs did not express LFA-3. However, the normal-appearing basal keratinocytes in epidermis overlying nests of BCC, did express ICAM-1, particularly when a marked LFA-1+ and LFA-2+ dermal lymphocytic infiltrate was present. After BCC tissue was incubated in vitro with IFN-gamma the expression of ICAM-1 was induced on 85% of tumors studied. Thus tumor cells did not possess an absolute inability to express adhesion molecules; rather the constitutive absence of such molecules may be due to insufficient in vivo cytokine levels necessary to induce expression or a barrier preventing cytokines from reaching and interacting with tumor cells. We conclude that the absence of ICAM-1 and LFA-3 adhesion molecules is a mechanism by which BCCs can avoid immunosurveillance.
Department of Dermatology, University of Michigan Medical School.
R S
RS
Taylor
C E
CE
Griffiths
M D
MD
Brown
N A
NA
Swanson
B J
BJ
Nickoloff
D000368:Aged; D000369:Aged, 80 and over; D000943:Antigens, Differentiation / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D018801:CD2 Antigens; D018968:CD58 Antigens; D002280:Basal Cell Carcinoma / Q000032:analysis* / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000032:analysis*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016169:Lymphocyte Function-Associated Antigen-1; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000032:analysis; D016028:Receptors, Leukocyte-Adhesion / Q000032:analysis; D012878:Skin Neoplasms / Q000032:analysis* / Q000276:immunology
D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D016028:Receptors, Leukocyte-Adhesion; D007371:Interferon-gamma