Berezhnaya N M
RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Vasylkivska 45, Kiev 03022, Ukraine.
Exp Oncol. 2010 Sep;32(3):159-66.
In present work the role of tumor cell biology upon different conditions of their interaction with the cells of immune system is discussed. The presented data show that it tumor cell biology that in many cases determines tumor antigen recognition and realization of cytotoxic action of killer cells. Here also we discuss own data obtained with the use of experimental tumor models (transplantable MC-rhabdomyosarcoma, B16 melanoma) and human tumors (soft tissue sarcoma, melanoma, breast cancer, ovarian cancer, cervical cancer). It was demonstrated that various tumors have different sensitivity to antitumor action of activated (LAK) and non-activated lymphocytes. Recent studies on the role of tumor cells in expansion and activity of different suppressor cells (MDSC, Treg, Th17, M-2 macrophages, etc.) are overviewed. The role of organ-specificity and interaction of the components of microenvironment (cells of immune system and stroma, tumor cells, endothelial cells, extracellular matrix) are discussed in details. Along with the presentation of modern views on some patterns that characterize the development of drug resistance of different tumors and capabilities of immune system cells to participate in lysis of resistant tumor cells, the authors present their own data illustrating that resistant tumor cells reveal increased sensitivity to LAK. An analysis of the involvement of a number of molecules, lymphocytes, and tumor cells in the phenomenon of elevated sensitivity to LAK action allowed to conclude that tumor cells reveal high sensitivity at the background of decreased E-cadherin expression and increased CD40 expression.
在当前工作中,讨论了肿瘤细胞生物学在其与免疫系统细胞相互作用的不同条件下所起的作用。所呈现的数据表明,在许多情况下,正是肿瘤细胞生物学决定了肿瘤抗原的识别以及杀伤细胞细胞毒性作用的实现。在此,我们还讨论了通过使用实验性肿瘤模型(可移植的MC-横纹肌肉瘤、B16黑色素瘤)和人类肿瘤(软组织肉瘤、黑色素瘤、乳腺癌、卵巢癌、宫颈癌)获得的我们自己的数据。已证明各种肿瘤对活化的(LAK)和未活化的淋巴细胞的抗肿瘤作用具有不同的敏感性。概述了近期关于肿瘤细胞在不同抑制细胞(MDSC、Treg、Th17、M-2巨噬细胞等)的扩增和活性中所起作用的研究。详细讨论了器官特异性以及微环境成分(免疫系统细胞和基质、肿瘤细胞、内皮细胞、细胞外基质)之间相互作用的作用。除了阐述关于表征不同肿瘤耐药性发展的一些模式以及免疫系统细胞参与裂解耐药肿瘤细胞能力的现代观点外,作者还展示了他们自己的数据,表明耐药肿瘤细胞对LAK表现出更高的敏感性。对多种分子、淋巴细胞和肿瘤细胞参与对LAK作用敏感性升高现象的分析得出结论,在E-钙黏蛋白表达降低和CD40表达增加的背景下,肿瘤细胞表现出高敏感性。