Heterogeneity and Plasticity of Immune Inflammatory Responses in the Tumor Microenvironment: Their Role in the Antitumor Effect and Tumor Aggressiveness

Abstract

This review considers the role that immune inflammatory responses (IIRs) play in tumor development and progression. Intratumoral IIR heterogeneity is presumably due to simultaneous differentiation and activation of certain T helper (Th) subpopulations and macrophages in various loci of the tumor, their phenotypic plasticity, and their antagonism of Th1 and Th2 responses. Evidence is provided to demonstrate that the IIR type in the tumor microenvironment determines the probability of the epithelial–mesenchymal transition (EMT), the emergence of invasive properties in tumor cells, the formation of tumor and premetastatic niches, and chemosensitivity. It is hypothesized that the effect of IIRs on tumor cells depends on the IIR type, which determines the cell and cytokine spectrum in the tumor microenvironment, rather than on the efficiency of specific immune responses to tumor antigens. Lastly, it is assumed that more efficient targets for IIR guidance are not provided by single molecules, but rather by the signaling pathways that can permanently prevent the Th2-type IIRs or suppress inflammatory reactions in the tumor.