Selectively down-regulated expression of major histocompatibility complex class I alleles in human solid tumors.
We studied the expression of major histocompatibility complex (MHC) class I molecule in 52 ex-vivo tumor samples comprising 29 ovarian, 15 lung, 1 breast, and 4 colon carcinomas; 1 midgut carcinoid; and 2 malignant mesenchymal tumors obtained from surgical specimens or from malignant effusions. The allelic products were visualized in untreated and interferon gamma + tumor necrosis factor alpha treated aliquots of tumor cells and in the patient's blood lymphocytes by the one-dimensional isoelectric focusing method. Generally, the tumor cells contained lower amounts of MHC class I molecules compared to the lymphocytes. In vitro exposure to interferon gamma and tumor necrosis factor alpha elevated the level of MHC class I expression in 24 of 52 tumors and corrected the assembly defect seen in 2 cases. In 20 tumors one or several human leukocyte antigen alleles were undetectable even after cytokine treatment. Correlation was seen with the grade of differentiation; the proportion of tumors with selective losses in poorly, moderately, or well differentiated tumors were 16 of 30, 3 of 13, and 1 of 9, respectively. Selective losses occurred in ovarian carcinoma cells collected from malignant effusions (12 of 22, 54%) but not in 7 primary tumors. In primary lung carcinomas the frequency was 36% (5 of 14 cases). Thirty-nine patients were serologically typed; thus the MHC alleles on the tumor cells could be identified. In this panel of tumors 30 human leukocyte antigen alleles were represented. Among these the expression of 15 was found to be down-regulated in some but not all tumors of the same histology.
Végh
Z
Z
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
Wang
P
P
Vánky
F
F
Klein
E
E
D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005805:Genes, MHC Class I / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007525:Isoelectric Focusing; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000502:physiology; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics* / Q000276:immunology; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma