Cytokines 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.