Tumor microenvironment (TME) creation is the consequence of these entities’ detrimental effects on the surrounding environment, which include attracting and corrupting non-malignant cells.
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The term “tumor microenvironment” (TME) describes the extracellular matrix, fibroblasts, immune cells, signaling molecules, resident and infiltrating host cells, secreted factors, proteins, tumor vasculature and lymphatics, pericytes, and occasionally adipocytes.
Tumor elimination, enhanced metastasis, or the creation of latent micrometastases are among the processes that the tight interaction between the tumor and the surrounding milieu is known to severely effect.
Novel treatments that specifically target elements of the environment are being developed since the TME influences the tumor’s resistance to therapy and its reaction to it. Many studies and developments are currently being carried out to better understand the connection between various tumor types and the TME in order to create novel, efficient therapies.
The following section discusses the main elements of the TME of the majority of human malignancies in relation to their significance for the initiation, progression, and response to therapy of cancer.
adipocytes
It has been shown that adipocytes in the TME help attract malignant cells by secreting adipokines and encourage the development of these cells by giving them fatty acids in cases of intra-abdominal cancers that metastasis to the omentum and certain other types of malignancies.
B-cells
Research has indicated that while B cells are mostly linked to the drainage of lymph nodes and the lymphoid structures next to the TME, they can also be discovered near the invasive edge of tumors. Studies indicate that a favorable outcome for ovarian and breast cancer is associated with B cell infiltration in the TME.
T cell
T cell presence is closely correlated with a favorable prognosis because these cells are often “experienced” with antigens and capable of eliminating malignant cells. Strong cytotoxic activity against several malignant cells, including cancer stem cells, has been associated with the presence of γδ T cells in the TME.
Nevertheless, the lack of experimental data has not been able to establish a positive or negative correlation between the presence of γδ T cells in the TME and prognosis.
Fibroblasts connected to cancer
Fibroblasts normally stimulate the process of organ fibrosis in response to tissue damage. On the other hand, it has been observed that fibroblasts in the TME increase the likelihood of developing cancer.
inflammatory cells (DCs)
The TME’s DCs are thought to be defective, unable to properly trigger the immune response to tumor-associated antigens, despite DCs’ usual ability to digest antigens. The prognosis is further adversely affected by the discovery that some DCs inhibit T cells.
Endocrine endothelial cells
Lymangiogenesis is stimulated by VEGFC or VEGFD produced by tumors. As a result, there is a proliferation of lymphatic endothelial cells in the TME and lymphatic tubes sprout, which aid in the spread of cancerous cells.
Additionally, an increasing amount of data indicates that the host immunological response to the tumor is modified by the lymphatic endothelial cells, hence physically modulating the TME.
DCs that are generated from myeloid cells (MDSCs)
Immune suppressor cells known as MDSCs are overexpressed in a large number of human malignancies. They may suppress T cell function, which indirectly deteriorates prognosis.
NK and NKT cells
When detected in the tumor microenvironment (TME) of colorectal, renal, gastric, liver, and lung malignancies, natural killer (NK) and natural killer T (NKT) cells are thought to indicate a favorable prognosis. On the other hand, other research indicates that NK cells may not be able to carry out their tumor-killing role in the TME because the presence of TGF-β, a transforming growth factor produced from malignant cells, activates their anergic phenotype.
Pristinetes
It is well established that pericytes, or perivascular stromal cells, are essential to the tumor vasculature, which supports the blood vessels structurally. Studies have demonstrated that less pericyte coverage of the vasculature in malignancies such bladder and colorectal are associated with a higher risk of metastases and tumor progression.
macrophages linked to tumors (TAMs)
In the majority of human malignancies, TAMs often have a pro-tumorigenic function, causing invasion, malignant cell migration, and metastasis. Preclinical and clinical evidence bolster the notion that a high concentration of TAMs in the TME is associated with a bad prognosis.
TANs, or tumor-associated neutrophils
While some research have come to the conclusion that TANs have a role in the development and metastasis of primary tumors, others are not so sure. A decrease in the immune system and enhanced angiogenesis have been linked to TANS, according to some study, whereas cytokine activation has been linked to TANs’ anticancer effects.
Endothelium vascular cells
The platelet-derived growth factors (PDGFs), VEGFs, FGFs, and chemokines found in the TME frequently activate endothelial cells and the pericytes that are linked with them. This mechanism promotes the spread of cancer and may result in the synthesis of angiogenic factors, which further facilitates the tumor’s development.