Abstract
Simple SummaryCytokines are small proteins that impact health and disease. They regulate cell signaling and have been shown to affect the immune response to various diseases, including cancer. Brain metastasis is a deadly disease. When cancer from the lungs, breast, or skin spreads to the brain, the survival of patients decreases. Therefore, understanding how cytokines affect and modulate the metastatic spread of cancer to the brain can help in improving diagnostic capabilities and therapeutic outcomes.Brain metastases are the most common of all intracranial tumors and a major cause of death in patients with cancer. Cytokines, including chemokines, interferons, interleukins, lymphokines, and tumor necrosis factors are key regulators in the formation of brain metastases. They regulate the infiltration of different cellular subsets into the tumor microenvironment and affect the therapeutic outcomes in patients. Elucidating the cancer cell-cytokine interactions in the setting of brain metastases is crucial for the development of more accurate diagnostics and efficacious therapies. In this review, we focus on cytokines that are found in the tumor microenvironment of brain metastases and elaborate on their trends of expression, regulation, and roles in cellular recruitment and tumorigenesis. We also explore how cytokines can alter the anti-tumor response in the context of brain metastases and discuss ways through which cytokine networks can be manipulated for diagnosis and treatment.
Highlights
Cytokines and chemokines are soluble signals that control the migration and positioning of cells in a specific microenvironment [1]
We focus on cytokines and chemokines that are found in the tumor microenvironment of lung, breast, and melanoma brain metastases; we elaborate on their trends of expression, regulation, and roles in cellular recruitment and tumorigenesis
The gene expression profiling of metastatic lung adenocarcinoma in the brain shows an increased expression of the receptor-binding cancer antigen expressed on SiSo cells (RCAS) and Fas ligand (FasL), which are present in neoplastic cells, induce apoptosis of natural killer (NK)/T cells, and play a role in immune evasion [23]
Summary
Cytokines and chemokines are soluble signals that control the migration and positioning of cells in a specific microenvironment [1]. Brain metastases are the most common malignant brain tumors and a major cause of death in patients with cancer They require the invasion of primary cancer cells from the lungs, breast, or skin, trafficking through the circulatory system, and the colonization of the brain parenchyma [5]. IGFBP7 VEGF CEMIP stromal cells, immune cells, and other cells within their surrounding microenvironment drive the various stages of metastasis [4] They mediate the brain response to metastatic cells by directing the trafficking of leukocytes into the tumor microenvironment. The migration of cells that express a specific chemokine receptor occurs across a chemokine gradient that allows cells to move toward high local concentrations of chemokines This migratory response is complex and consists of diverse leukocyte subsets with both antitumor and pro-tumorigenic activities [6]. We explore how these cytokines alter the anti-tumor response and discuss ways through which chemokine networks can be used for potential treatments
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