Insights Into Mechanisms of Tumor and Immune System Interaction: Association With Wound Healing

Abstract

A large number of studies have presented a great deal of information about tumor and immune system interaction. Nevertheless, the problem of tumor evasion from the immune reaction is still difficult to resolve. Understanding the ways in which immunosuppressive tumor microenvironment develops and maintains its potential is of utmost importance to ensure the best use of the suppressed immune functions. The study presents a review covering the data on tumor-associated antigens, mechanisms of tumor evasion from the immune reactions, and search for common immunosuppressive processes of tumor growth and normal wound healing. The study discusses the important role of monocytes/macrophages in the regulation of immune system reactions. We suggest that the simultaneous actions of growth factors and pro-inflammatory cytokines may result in the suppression of the immune system. The study describes intracellular signaling molecules that take part in the regulation of the myeloid cell functions. If the hypothesis is proved correct, the indicated interaction of cytokines could be regarded as a prospective target for antitumor therapy.

Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy

“…Esophageal cancer TME is a very dynamic and complex ecosystem entailing cellular components (cancer-associated fibroblasts (CAFs), immune cells, endothelial cells, pericytes, adipocytes), extracellular matrix proteins (collagen, elastin fibers, fibronectins, proteoglycans, hyaluronic acid, osteopontin, periostin, and SPARC (secreted protein acidic and rich in cysteine, also known as osteonectin or BM-40) and secretory proteins including cytokines, chemokines and many growth factors secreted by tumor and stromal cells. The TME is also infiltrated by immunosuppressive cells, such as regulatory T (Treg) cells, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) [ 24 , 25 ].. Cancer cells are known to secrete several soluble factors, including cytokines, chemokines, and growth factors, which help the immune cells reprogram the surrounding microenvironment to promote tumor growth, metastasis, and resistance to CRT. In advanced tumors, various chemokines and pro-inflammatory cytokines that promote cancer are abundant, whereas cytokines that inhibit tumor growth are usually lacking [ 26 – 28 ].…”

Modeling the tumor immune microenvironment for drug discovery using 3D culture

“…Given that the Treg cell mechanism of action depends on DCs and macrophages, these other cell types are also being pursued as therapeutic targets for releasing immune suppression. 40 …”

“… 46 Tumor-associated macrophages (TAMs), however, are generally M2-type macrophages that inhibit inflammation, which suppresses immunity to promote cancer progression. 40 Given that tumors behave similar to “wounds that do not heal,” 47,48 they readily co-opt the immunosuppressive wound healing activities of M2 macrophages that normally prevent tissue damage from prolonged immune activation. 46 TAMs can be recruited into tumors by chemokines such as CCL2, CCL3, CCL4, CXCL12, IL-6, and IL-1β.…”

Nanomedicine-based drug delivery towards tumor biological and immunological microenvironment

“…Increased levels of immunosuppressive cytokines, such as TGF -β and IL-10, are accumulated in the tumor microenvironment 183 . These cytokines are involved in a variety of activities in tumorigenesis and play important roles in the chronic inflammation processes 184 , 185 .…”