Inflammatory Tumor Microenvironment: Role of Cytokines and Virokines in Breast Cancer Progression and Metastasis

The breast tumor microenvironment (TME) is composed of cellular components (e.g., cancer cells, immune cells, endothelial cells, fibroblasts, mast cells) and non-cellular components (e.g., extracellular matrix proteins, cytokines, chemokines, signal molecules), and it differs significantly from the normal tissue microenvironment in terms of low vascular density, hypoxia, weak acidity, and reducibility. Other extrinsic components, like the microbiome and virome, also play a role in the changes in the breast TME. Chronic inflammation, in particular, maintains local homeostasis balance and builds the inflammatory TME, which offers circumstances for breast cancer cell progression. Chronic inflammation and immunosuppression in the inflammatory milieu can result in the overexpression of inflammatory mediators and the infiltration of immune cells such as macrophages and neutrophils, which generally signals tumor development. Breast cancer cells control the function of TME components via the expression of cytokines that can increase self-proliferation, growth, and treatment resistance in an autocrine form, and encourage recruitment, activation, and differentiation of other cells in the TME in a paracrine approach as IL-6, IL-8, and even VEGF. Even though these cytokines frequently alert immune cells to the presence of infections and tissue damage, these cytokines drive immune cells to express additional cytokines that function in both autocrine and paracrine pathways, resulting in a chronic inflammatory state that promotes cancer progression. Oncomodulatory viruses, such as human cytomegalovirus (HCMV), have been demonstrated in recent research to influence the pathophysiology of breast cancers by influencing cell signaling, cell metabolism, apoptosis, angiogenesis, cell-cell communication, inflammation, and antitumor immune suppression. Several virokines are released into the TME, and these viral proteins, such as viral interleukin-6 (vIL-6) encoded only by HHV8, and viral chemokine or IL-10 homologs generated by HCMV, influence tumor progression. Previous research has shown that TME has aberrant activities and plays an important role in tumor growth, which is one of the main reasons why "cancer cell centric" treatments are unsuccessful.

The connection between inflammation and breast cancer poor prognosis and metastasis is not completely understood. Recent studies suggests that the critical components of breast cancer-related inflammation work together in a coordinated manner to control its progression, which might help in the development of novel anticancer medicines. As a result, inflammatory cytokines are the most effective targets in breast cancer treatment. Nonetheless, additional research is needed to investigate the hidden function of oncomodulatory viruses and their expressed virokines in the inflammatory microenvironment of breast cancer. The purpose of this research topic is to better recognize the potential involvement of inflammatory cytokines and virokines in the progression and metastasis of breast cancer.

The scope of this research topic is to highlight the potential role of inflammatory TME in breast cancer progression and metastasis. We will welcome Original Research Articles, Reviews, and Mini-Reviews related to the following Topics:

• Molecular mechanisms underlining breast cancer inflammatory microenvironment.
• Inflammatory cytokines as regulators to breast cancer poor prognosis.
• Links between inflammation and breast cancer metastasis.
• Crosstalk between different cells within the TME
• Genetic alterations/instabilities affecting breast cancer inflammatory microenvironment.
• Potential role of the microbiome in breast inflammatory TME.
• Role of oncomodulatory viruses and their expressed virokines in breast cancer metastatic cascade.

Please note: studies consisting solely of bioinformatic investigation of publicly available genomic/transcriptomic/proteomic data do not fall within the scope of the section unless they are expanded and provide significant biological or mechanistic insight into the process being studied.