Selective upregulation of MHC class I expression in metastatic colonies derived from tumor clones of a murine fibrosarcoma.
Eighteen metastatic nodes derived from the wild-type (GR9) and from 4 different clones (G2, D8, B10, and B9) obtained from a fibrosarcoma were analyzed for H-2 class I and II expression, as well as for adhesion molecules (CD44, CDIIb, CD18, CD49, and CD54). When metastatic nodes were cultured, typed for H-2 antigens, and compared with the H-2 expression of the inducing tumor cell, H-2 Kd and Dd class I expression was greater in most nodes analyzed. In contrast, the Ld molecule remained negative, or showed a minor increase. Class II expression was negative in the wild-type and the tumor clones, and remained so in the metastatic colonies. Analysis of the adhesion molecules revealed no differences between the inducing tumor cells and the metastatic nodes. The only molecule expressed was CD44, which was present in all cells studied and was also inducible by interferon-gamma. The increase in H-2K and H-2D expression was associated with resistance to natural killer cytotoxicity, as observed in the G2 tumor clone and some autologous metastases, such as B9MP2, G2MK2, and G2MLI. In three independent clones of this tumor system (D8, BIOMP6, and B9MP6) we found that tumor cells treated with interferon-gamma had the same altered phenotype, i.e., a selective lack of response of the Ld molecule to induction. These findings add a cautionary note to the well-established idea that tumor cells may lose all class I antigens during tumor progression, and suggest that sometimes this may not be the case. The selective downregulation of Ld and upregulation of Kd and Dd class I expression may give some tumor cells means of escaping both cytotoxic lymphocyte and natural killer immune surveillance.
Pedrinaci
S
S
Department of Analisis Clinicos, Hospital Universitario Virgen Nieves, Universidad De Granada, Spain.
Algarra
I
I
Garcia Lora
A
A
Gaforio
J J
JJ
Perez
M
M
Garrido
F
F
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D018821:CD18 Antigens / Q000032:analysis / Q000276:immunology; D002860:Chromium Radioisotopes; D002999:Clone Cells; D005354:Fibrosarcoma / Q000737:chemistry / Q000276:immunology* / Q000556:secondary; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D018960:Hyaluronan Receptors / Q000032:analysis / Q000276:immunology; D039441:Integrin alpha4; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000032:analysis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D012983:Soft Tissue Neoplasms / Q000737:chemistry / Q000276:immunology* / Q000556:secondary; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; D000970:Antineoplastic Agents; D018821:CD18 Antigens; D002860:Chromium Radioisotopes; D015395:Histocompatibility Antigens Class I; D018960:Hyaluronan Receptors; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1; D039441:Integrin alpha4; D007371:Interferon-gamma