Taramelli D, Fossati G, Mazzocchi A, Delia D, Ferrone S, Parmiani G
Cancer Res. 1986 Jan;46(1):433-9.
Human melanoma cells freshly isolated from 20 patients with primary and 73 patients with metastatic melanomas were analyzed by indirect immunofluorescence staining with monoclonal antibodies (MoAb) to class I (HLA-A, -B, and -C) and class II (HLA-DR and -DQ) antigens and to melanoma associated antigen (MAA). The latter included the GD3-MAA and the high molecular weight MAA. HLA class I antigens were present in 91 and 93% of primary and metastatic tumors, respectively. GD3-MAA was detected in 100% of primary and 80% of metastatic tumors. Whereas the high molecular weight MAA was expressed in 75% of tumors. Sixty % of primary and 50% of metastatic melanomas were stained by anti-HLA-DR MoAb, whereas 38 and 21% of cases, respectively, were stained by anti-HLA-DQ MoAb. Marked phenotypic heterogeneity was evident among primary and metastatic tumors, including different metastases from the same patient. Moreover, in vitro culture of melanoma cells isolated from metastases was associated with an increase from 50 to 75% of tumors stained by anti-HLA-DR MoAb but not of tumors positive for HLA class I antigens and MAA. In vitro incubation with partially purified or recombinant human gamma-interferon enhanced the expression of HLA-DR antigens on all short-term cultured melanoma cells tested but induced and/or augmented the expression of HLA-DQ antigens only in 5 of the 8 cases examined. The average increase in antigenic expression was higher for HLA-DQ than for HLA-DR antigens. Flow cytometric measurement of DNA content of melanoma cells treated with gamma-interferon revealed that the increase of HLA-DR and -DQ expression induced by gamma-interferon was independent from the cell cycle of the tumor cells.
采用针对I类(HLA-A、-B和-C)和II类(HLA-DR和-DQ)抗原以及黑色素瘤相关抗原(MAA)的单克隆抗体(MoAb)进行间接免疫荧光染色,对从20例原发性黑色素瘤患者和73例转移性黑色素瘤患者新鲜分离的人黑色素瘤细胞进行了分析。后者包括GD3-MAA和高分子量MAA。I类HLA抗原分别存在于91%的原发性肿瘤和93%的转移性肿瘤中。GD3-MAA在100%的原发性肿瘤和80%的转移性肿瘤中被检测到。而高分子量MAA在75%的肿瘤中表达。60%的原发性黑色素瘤和50%的转移性黑色素瘤被抗HLA-DR MoAb染色,而分别有38%和21%的病例被抗HLA-DQ MoAb染色。原发性和转移性肿瘤之间存在明显的表型异质性,包括同一患者的不同转移灶。此外,从转移灶分离的黑色素瘤细胞的体外培养与抗HLA-DR MoAb染色的肿瘤比例从50%增加到75%相关,但与I类HLA抗原和MAA阳性的肿瘤无关。用部分纯化或重组人γ干扰素进行体外孵育可增强所有测试的短期培养黑色素瘤细胞上HLA-DR抗原的表达,但仅在8例检测病例中的5例中诱导和/或增强了HLA-DQ抗原的表达。HLA-DQ抗原表达的平均增加高于HLA-DR抗原。对用γ干扰素处理的黑色素瘤细胞的DNA含量进行流式细胞术测量发现,γ干扰素诱导的HLA-DR和-DQ表达增加与肿瘤细胞的细胞周期无关。