Complexity of Tumor Microenvironment: a Major Culprit in Cancer Development

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Background

Tumor microenvironment (TME) is a complicated system containing a variety of elements, including infiltrating immune cells, tumor-related stromal cells, endothelial cells, and extracellular matrix. Understanding cellular and molecular insights of the tumor microenvironment are very useful for the diagnosis, treatment, and prognosis of cancers. TME is involved in the gene expression and molecular functions of tumor cells, which is closely related to the response to immunotherapies. There is increasing evidence showing that the infiltrating immune cells such as T cells, B cells, macrophages, dendritic cells, monocytes, neutrophils, and mast cells can regulate cancer development and progression. Tumor cells in the TME can invade surrounding tissues or metastasize through lymphatic vessels and blood and the infiltrated cells can stimulate host immune response for releasing cytokines, cytokine receptors, and other factors, which directly or indirectly promote or inhibit tumor cell proliferation. Recently, attention has been paid to the tumor microenvironment (TME), which plays a vital role in the occurrence and development of cancer. Recent studies have shown that tumor immune cell infiltration (ICI) is associated with the clinical outcomes of cancer patients such as osteosarcoma, gastric cancer, and liver cancer. Extensive research on the TME has shown that infiltrating immune cells play a vital role in tumor spread, recurrence, metastasis, and the response to immunotherapy. However, the detailed profile of immune cells infiltration and differentially expressed genes (Metabolic, immune-related, or others) in many cancers have not been elucidated. There are many intriguing pieces of evidence to confirm the involvement of metabolic factors in certain cancer pathogenesis and progression. Likewise, prostate tumors specifically rely on the lipids for initial growth and often use de novo lipid synthesis to produce fatty acids. Importantly, The metabolic health of the individuals fuels further tumor growth and metastasis. Furthermore, the metabolic health of the individuals may influence the prognosis and treatment of the cancers, for example, androgen deprivation therapy (ADT), first-line therapy in prostate cancer, induces remarkable positive metabolic changes. Hence, metabolic health can influence the overall survival of the patients.

Furthermore, studying genetic and other factors involved in the metabolic, endocrine, and immune functions in cancer or tumor microenvironment can provide a better understanding of underlying mechanisms of cancer development and progression. The differential expression of these factors and infiltrating cells in different tumors and normal controls have great importance for identifying prognostic targets. The recent advancement in cancer therapy improves the treatment outcomes by hormones therapy and immunotherapy such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T-cell adoptive immunotherapy; A type of treatment in which T cells are taken from the patients and changed in the laboratory (adding special targets that bind with a specific receptor) so they will attack cancer cells. Nevertheless, patients with advanced-stage or unfavorable malignant tumors still face a poor prognosis and recurrence, and the CAR-T therapy remains limited by the lack of ideal or appropriate targets in solid tumors. Thus, more and more comprehensive studies related to genetic regulation of tumors through metabolic and endocrine factors, immune cell infiltration, and immune functions are being done to identify the related biomarkers and underlying mechanisms in cancer development and progression, thus ultimately can be used in targeted therapy.

The aim of the current special issue is to collect research articles, short communications, case reports, reviews, and comprehensive bioinformatics data papers related to the tumor microenvironment, regulation of cancers through metabolic and endocrine factors, immune cells and immune checkpoint inhibitors, tumor heterogeneity and cells infiltration in TME, transcriptional and post translational regulation of factors in TME and other articles related to proposed topic will be considered for peer review and publication.

Keywords: Tumor Microenvironment, Cancer Development, Immune cell infiltration, Tumor heterogeneity, Metabolic genes, Immune function, immunotherapy

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