Santin A D, Hermonat P L, Ravaggi A, Chiriva-Internati M, Hiserodt J C, Pecorelli S, Parham G P
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology,University of Arkansas, Little Rock, Arkansas, 72205, USA.
Gynecol Oncol. 1998 Aug;70(2):195-201. doi: 10.1006/gyno.1998.5060.
Radiation treatment is one of the most standardized and effective modalities for contemporary cervical cancer therapy. In addition, the radiation-potentiating effects of retinoic acid have been recently described. In order to investigate whether enhanced immunogenicity might be responsible for such potentiation, we have evaluated the effects of retinoic acid combined with high doses of gamma-irradiation on the expression of major histocompatibility complex (MHC) Class I and II and intercellular adhesion molecule-1 (ICAM-1) in human cervical carcinoma cell lines.
The expression of surface antigens (MHC Class I and II and ICAM-1) was evaluated by FACS analysis in untreated control cells and in cells following their exposure to retinoic acid, high doses of gamma-irradiation (i.e., 5000 and 10,000 cGy), or the combination of the two procedures.
HT-3 and SiHa cervical cancer cells expressed variable levels of MHC Class I and ICAM-1 antigens while Class II surface antigens were not detectable. Exposure to either 5000 or 10,000 cGy completely inhibited cell replication in both cell lines and significantly and consistently increased the expression of all surface antigens present on the cells prior to irradiation. Irradiation was unable to induce neoexpression of antigens previously not expressed by these cells (i.e., MHC Class II). In a similar fashion, retinoic acid was also able to significantly increase the expression of MHC Class I and ICAM-1 antigens when compared to untreated tumor cells but was not able to induce the expression of HLA Class II surface antigens. Exposure to the combination of radiation plus retinoic acid significantly upregulated HLA Class I and ICAM-1 molecules in an additive manner when compared to the levels obtainable with the exposure to radiation or retinoic acid alone.
These data indicate that the combination of these two treatments could induce an additive effect on the expression of immunologically important surface antigens in human cervical cancer cells. These findings, together with the powerful antiproliferative effect of retinoids and irradiation on tumor cells, suggest that the combined regimen may be a promising and more effective combination for the treatment of cervical cancer.
放射治疗是当代宫颈癌治疗中最标准化且有效的治疗方式之一。此外，最近有报道称维甲酸具有放射增敏作用。为了研究免疫原性增强是否可能是这种增敏作用的原因，我们评估了维甲酸联合高剂量γ射线照射对人宫颈癌细胞系中主要组织相容性复合体（MHC）I类和II类以及细胞间黏附分子-1（ICAM-1）表达的影响。
通过流式细胞术分析评估未处理的对照细胞以及暴露于维甲酸、高剂量γ射线照射（即5000和10000 cGy）或两种处理方法联合后的细胞表面抗原（MHC I类和II类以及ICAM-1）的表达。
HT-3和SiHa宫颈癌细胞表达不同水平的MHC I类和ICAM-1抗原，而未检测到II类表面抗原。暴露于5000或10000 cGy均可完全抑制这两种细胞系中的细胞增殖，并显著且持续增加照射前细胞上所有表面抗原的表达。照射无法诱导这些细胞先前未表达的抗原（即MHC II类）的新表达。同样，与未处理的肿瘤细胞相比，维甲酸也能够显著增加MHC I类和ICAM-1抗原的表达，但无法诱导HLA II类表面抗原的表达。与单独暴露于辐射或维甲酸所获得的水平相比，暴露于辐射加维甲酸的组合显著上调了HLA I类和ICAM-1分子，呈相加效应。
这些数据表明，这两种治疗方法的联合可对人宫颈癌细胞中具有免疫重要性的表面抗原的表达产生相加效应。这些发现，连同维甲酸和照射对肿瘤细胞强大的抗增殖作用，表明联合方案可能是一种有前景且更有效的宫颈癌治疗组合。
