Tashireva L A, Perelmuter V M, Manskikh V N, Denisov E V, Savelieva O E, Kaygorodova E V, Zavyalova M V
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, Russia.
Biochemistry (Mosc). 2017 May;82(5):542-555. doi: 10.1134/S0006297917050029.
Inflammatory infiltration of tumor stroma is an integral reflection of reactions that develop in response to any damage to tumor cells including immune responses to antigens or necrosis caused by vascular disorders. In this review, we use the term "immune-inflammatory response" (IIR) that allows us to give an integral assessment of the cellular composition of the tumor microenvironment. Two main types of IIRs are discussed: type 1 and 2 T-helper reactions (Th1 and Th2), as well as their inducers: immunosuppressive responses and reactions mediated by Th22 and Th17 lymphocytes and capable of modifying the main types of IIRs. Cellular and molecular manifestations of each IIR type are analyzed and their general characteristics and roles in tissue regeneration and tumor growth are presented. Since inflammatory responses in a tumor can also be initiated by innate immunity mechanisms, special attention is given to inflammation based on them. We emphasize that processes accompanying tissue regeneration are prototypes of processes underlying cancer progression, and these processes have the same cellular and molecular substrates. We focus on evidence that tumor progression is mainly contributed by processes specific for the second phase of "wound healing" that are based on the Th2-type IIR. We emphasize that the effect of various types of immune and stroma cells on tumor progression is determined by the ability of the cells and their cytokines to promote or prevent the development of Th1- or Th2-type of IIR. Finally, we supposed that the nonspecific influence on the tumor caused by the cytokine context of the Th1- or Th2-type microenvironment should play a decisive role for suppression or stimulation of tumor growth and metastasis.
肿瘤基质的炎性浸润是对肿瘤细胞任何损伤所产生反应的整体反映，包括对抗原的免疫反应或血管紊乱引起的坏死。在本综述中，我们使用“免疫炎症反应”（IIR）这一术语，以便对肿瘤微环境的细胞组成进行整体评估。本文讨论了两种主要类型的IIR：1型和2型辅助性T细胞反应（Th1和Th2），以及它们的诱导剂：免疫抑制反应和由Th22和Th17淋巴细胞介导的、能够改变主要IIR类型的反应。分析了每种IIR类型的细胞和分子表现，并阐述了它们的一般特征以及在组织再生和肿瘤生长中的作用。由于肿瘤中的炎症反应也可由先天免疫机制引发，因此特别关注基于这些机制的炎症。我们强调，组织再生过程是癌症进展潜在过程的原型，且这些过程具有相同的细胞和分子底物。我们关注的证据表明，肿瘤进展主要由基于Th2型IIR的“伤口愈合”第二阶段特有的过程所致。我们强调，各种类型的免疫细胞和基质细胞对肿瘤进展的影响取决于细胞及其细胞因子促进或阻止Th1或Th2型IIR发展的能力。最后，我们推测Th1或Th2型微环境的细胞因子背景对肿瘤产生的非特异性影响应在抑制或刺激肿瘤生长及转移方面起决定性作用。
