Scupoli M T, Sartoris S, Tosi G, Ennas M G, Nicolis M, Cestari T, Zamboni G, Martignoni G, Lemoine N R, Scarpa A, Accolla R S
Istituto di Immunologia e Malattie Infettive, Università di Verona, Italy.
Tissue Antigens. 1996 Oct;48(4 Pt 1):301-11. doi: 10.1111/j.1399-0039.1996.tb02649.x.
The antigens encoded by the major histocompatibility complex (MHC) are cell surface glycoproteins that play a fundamental role in the regulation of the immune response. Anomalous MHC expression in tumor cells has been viewed as an important feature to escape tumor recognition by immune cells. Low or absent MHC class I expression as well as ectopic MHC class II expression have been often observed to correlate with high grade malignancy and metastatic potential in a variety of human cancers. To date, very little investigation of MHC (HLA in man) class I and class II expression in human pancreatic cancer has been reported. We investigated this aspect on frozen sections of 8 pancreatic adenocarcinomas and 18 established in vitro cell lines. HLA class I was expressed in all but two cancers whereas de novo HLA class II expression was detected in 3 of 8 cancers. Interestingly, a hierarchy in the expression of the various subsets of HLA class II was found with HLA- DR > -DP > -DQ. Results on cell lines strongly resembled the ones obtained in cancer tissues. However, a peculiar feature was observed in certain cell lines. HLA class II antigens were expressed in only a few cell lines and in some of them a mixed population of positive and negative cells was found. Sorting and cloning of the two populations confirmed the existence of tumor cell clones with stable and distinct HLA class II phenotype. Taken together, these results indicate the cellular heterogeneity of pancreatic cancer cells with regard to the qualitative and quantitative expression of major histocompatibility complex genes, and may provide new insights for a better understanding of the tumorhost relationships in this extremely severe form of neoplasia.
主要组织相容性复合体（MHC）编码的抗原是细胞表面糖蛋白，在免疫反应调节中起基本作用。肿瘤细胞中MHC表达异常被视为逃避免疫细胞对肿瘤识别的一个重要特征。在多种人类癌症中，经常观察到MHC I类表达降低或缺失以及MHC II类异位表达与高分级恶性肿瘤和转移潜能相关。迄今为止，关于人类胰腺癌中MHC（人类为HLA）I类和II类表达的研究报道很少。我们在8例胰腺腺癌的冰冻切片和18种已建立的体外细胞系上研究了这一方面。除两例癌症外，所有癌症均表达HLA I类，而在8例癌症中有3例检测到从头开始的HLA II类表达。有趣的是，发现HLA II类各亚群的表达存在层次结构，即HLA-DR > -DP > -DQ。细胞系的结果与在癌组织中获得的结果非常相似。然而，在某些细胞系中观察到一个特殊特征。HLA II类抗原仅在少数细胞系中表达，并且在其中一些细胞系中发现了阳性和阴性细胞的混合群体。对这两个群体进行分选和克隆证实了具有稳定且不同HLA II类表型的肿瘤细胞克隆的存在。综上所述，这些结果表明胰腺癌细胞在主要组织相容性复合体基因的定性和定量表达方面具有细胞异质性，并可能为更好地理解这种极其严重的肿瘤形式中的肿瘤-宿主关系提供新的见解。
