Ben-Hur Herzl, Kossoy George, Zandbank Judit, Zusman Itshak
Laboratory of Experimental Medicine affiliated to the Institute of Pathology, Tserifin, Israel.
Int J Mol Med. 2002 Apr;9(4):425-30.
We have shown previously that soluble low-molecular-mass tumor-associated antigens (sTAA) promote the anti-tumor effect of the anticancer drug cyclophosphamide (CPA) on rat mammary carcinogenesis. In this study, we analyzed the possible mechanism underlying this phenomenon. Studies were performed on tumors obtained from the following groups of mammary tumor-bearing rats: i) control rats, ii) rats treated with sTAA, iii) rats treated with CPA, iv) rats treated with CPA and sTAA. All analyzed tumors represented different types of invasive duct carcinomas. The rate of lymphoid infiltration and T cell content (CD4+ and CD8+ cells) of tumors were analyzed immunohistochemically. In parallel, mitotic index was evaluated in tumor cells. In tumor-bearing rats, high lymphoid proliferation was found at the periphery of tumors, and to a lesser extent deep inside the tumors. In control tumors, CD4+ T cell content was very low whereas CD8+ cells were highly abundant, especially at the tumor periphery. Treatment with sTAA significantly increased the total number of lymph cells and the number of CD8+ lymphocytes inside the tumors. Cytoplasmic vacuolization, decreased mitotic index and various degrees of fibrosis were the most distinct changes in tumors treated with CPA alone. CPA also sharply decreased the activity of all lymph cells studied, especially of CD4+ lymphocytes which could no longer be observed following this treatment. The combined treatment of CPA and sTAA increased the number of lymph cells, although they did not reach control levels. Inhibition of mainly CD4+ lymphocyte synthesis of CPA was confirmed by the low CD4/CD8 ratio, which increased slightly after the combined treatment with CPA and sTAA. Findings in the present study demonstrate that vaccination with sTAA actively promotes the generation of the host's antitumor immune response.
我们之前已经表明，可溶性低分子量肿瘤相关抗原（sTAA）可促进抗癌药物环磷酰胺（CPA）对大鼠乳腺癌发生的抗肿瘤作用。在本研究中，我们分析了这一现象背后的可能机制。对从以下几组患乳腺肿瘤的大鼠获得的肿瘤进行了研究：i）对照大鼠，ii）用sTAA治疗的大鼠，iii）用CPA治疗的大鼠，iv）用CPA和sTAA治疗的大鼠。所有分析的肿瘤均代表不同类型的浸润性导管癌。通过免疫组织化学分析肿瘤的淋巴细胞浸润率和T细胞含量（CD4 +和CD8 +细胞）。同时，评估肿瘤细胞中的有丝分裂指数。在患肿瘤的大鼠中，在肿瘤周边发现高淋巴细胞增殖，在肿瘤内部深处程度较轻。在对照肿瘤中，CD4 + T细胞含量非常低，而CD8 +细胞高度丰富，尤其是在肿瘤周边。用sTAA治疗显著增加了肿瘤内淋巴细胞总数和CD8 +淋巴细胞数量。单独用CPA治疗的肿瘤中，细胞质空泡化、有丝分裂指数降低和不同程度的纤维化是最明显的变化。CPA还显著降低了所有研究的淋巴细胞活性，尤其是CD4 +淋巴细胞，在这种治疗后无法再观察到。CPA和sTAA联合治疗增加了淋巴细胞数量，尽管未达到对照水平。低CD4/CD8比值证实了CPA主要抑制CD4 +淋巴细胞的合成，在CPA和sTAA联合治疗后略有增加。本研究结果表明，用sTAA进行疫苗接种可积极促进宿主抗肿瘤免疫反应的产生。
