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REVIEW: Types of Immune-Inflammatory Responses as a Reflection of Cell–Cell Interactions under Conditions of Tissue Regeneration and Tumor Growth

L. A. Tashireva1, V. M. Perelmuter1, V. N. Manskikh2, E. V. Denisov1*, O. E. Savelieva1, E. V. Kaygorodova1, and M. V. Zavyalova1,3

1Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, Russia; E-mail: d_evgeniy@oncology.tomsk.ru

2Lomonosov Moscow State University, 119991 Moscow, Russia

3Siberian State Medical University, 634050 Tomsk, Russia

* To whom correspondence should be addressed.

Received October 7, 2016; Revision received November 24, 2016
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.
KEY WORDS: immune-inflammatory response, lymphocyte subpopulations, macrophages, fibroblasts, tissue regeneration, tumor progression

DOI: 10.1134/S0006297917050029