Seljelid R, Jozefowski S, Sveinbjörnsson B
Department of Experimental Pathology, Medical Faculty, University of Tromsø, Norway.
Anticancer Res. 1999 Nov-Dec;19(6A):4809-22.
The accumulated evidence indicates that tumor stroma with its cells and cell products plays a much more active and important role than previously believed. Growth factors and cytokines produced by macrophages and other cells are crucial for stroma formation and angiogenesis. Lytic enzymes provided by stromal cells may be essential for invasion. TNF and other inflammatory mediators may be operative in the systemic effects of tumors, e.g. cachexia. All these effects may come about through the action of soluble substances produced by tumor cells or by more intimate interactions. There is no evidence that stromal cells are directly involved in carcinogenesis--i.e. the cellular transformation to produce the malignant cell. On the other hand, stromal cells and other components of the interstitia are instrumental in tumorigenesis--i.e. the development of a real malignant tumor from its start on the cellular or subcellular level. In one way of looking at it, the stromal cells, e.g. macrophages may be considered as "slaves", kept to carry out certain functions, synthesize essential substances e.g. growth factors that the tumor cells do not have the capacity or the degree of finely tuned machinery to produce. The objective of immunomodulation should then be to create a "slave uprising", to make the macrophages and other cells turn against their masters, stop producing growth factors and start producing harmful factors that would lead to the elimination of the malignant growth. The first target of immunomodulation in tumor disease should probably be local malignancies where no effective treatment exists today- and selected cases of metastatic prevention (181, 182).
越来越多的证据表明，肿瘤基质及其细胞和细胞产物所起的作用比之前认为的更加积极和重要。巨噬细胞和其他细胞产生的生长因子和细胞因子对基质形成和血管生成至关重要。基质细胞提供的溶解酶可能对肿瘤侵袭至关重要。肿瘤坏死因子和其他炎症介质可能在肿瘤的全身效应（如恶病质）中起作用。所有这些效应可能是通过肿瘤细胞产生的可溶性物质的作用或更密切的相互作用而产生的。没有证据表明基质细胞直接参与致癌作用——即细胞转化产生恶性细胞。另一方面，基质细胞和间质的其他成分在肿瘤发生过程中起重要作用——即从细胞或亚细胞水平开始发展成真正的恶性肿瘤。从某种角度来看，基质细胞，如巨噬细胞，可能被视为“奴隶”，被保留下来执行某些功能，合成肿瘤细胞没有能力或没有精细调节机制来产生的必需物质，如生长因子。免疫调节的目标应该是引发一场“奴隶起义”，使巨噬细胞和其他细胞反抗它们的主人，停止产生生长因子，开始产生有害因子，从而导致消除恶性肿瘤生长。肿瘤疾病免疫调节的首要目标可能应该是针对目前尚无有效治疗方法的局部恶性肿瘤，以及某些预防转移的病例（参考文献181、182）。
