Медицинская иммунология (Apr 2020)
Tumor microenvironment: the formation of the immune profile
Abstract
Tumor microenvironment (TME) is formed as a result of interaction and cross-linking between the tumor cell and different types of surrounding cells. Recent studies have shown that the tumor reprograms the microenvironment so that TME promotes the development of primary tumors, their metastasis and becomes an important regulator of oncogenesis. Under the influence of the tumor, the immune profile in the TME undergoes significant changes, “editing". An immunosuppressive network is formed, which suppresses the activity of the main effector of cellular immunity — T lymphocytes. T cells in TMA are in a state of anergy and exhaustion. T cells in TME are characterized by increased expression of inhibitory receptors, decreased secretion of cytokines and cytolytic activity. Blocking inhibitory receptors with specific antibodies can lead to the restoration of the functions of exausted T cells. Therefore, the restoration of the functional activity of T lymphocytes is one of the important strategies in cancer immunotherapy. The formation of the immune profile is influenced by genetic aberrations accumulating in the tumor. They play an important role in creating a specific, characteristic only for this tumor immune environment in the TME. Genetic changes in tumor cells lead to phenotypic and functional rearrangements of lymphocytes, which allows the tumor to escape the reaction of immune cells. Since many tumors occur after prolonged inflammation or exhibit characteristics of chronic inflammation as they progress, inflammation is considered an important factor in the formation of immune profile in TME. Immune infiltrates from different human tumors associated with inflammation may contain valuable prognostic and pathophysiological information. Macrophages in the TME now began to be regarded as descriptive marker and as a therapeutic target. One of the main mechanisms by which tumor cells reprogram surrounding cells is the release of exosomes — small vesicles that carry and deliver proteins and nucleic acids to other cells. When exosomal cargo is absorbed, molecular, transcriptional and translational changes occur in the recipient non-tumor cells in the TME. Therefore, tumor exosomes are an effective means by which the functions of immune cells in TME are purposefully changed. Thus, along with individual molecular and genomic testing of the tumor, attention should be paid to a deeper analysis of the immune profile of TME. It is a large resource of biomarkers and targets for immunotherapy.
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