Dynamics of inflammatory signals within the tumor microenvironment

Table 1 Players in the immunosuppressive milieu and their roles

Immune cells/cytokines	Role in tumorigenesis
Regulatory T cells	Suppress anti-tumor immune responses, contributing to immune tolerance of tumor cells
Myeloid-derived suppressor cells	Inhibit T-cell function, promote tumor progression by creating a pro-tumoral environment
Tumor-associated macrophages	Support tumor growth and metastasis through cytokine release and immune suppression
Transforming growth factor beta	Inhibits cytotoxic T cells and natural killer cells; promotes extracellular matrix remodeling and metastasis
Interleukin-10	Inhibits anti-tumor immunity and contributes to an immunosuppressive microenvironment
Vascular endothelial growth factor	Promotes angiogenesis, providing nutrients and oxygen to tumors
Programmed death-ligand 1	Interacts with programmed death-1 on T cells, leading to immune exhaustion and preventing T cells from attacking tumors

Table 2 Summary of the roles of cancer-associated fibroblasts and tumor-associated macrophages in tumor growth and immunosuppression

Key players	Roles and mechanisms in tumor microenvironment	Impact on tumor progression
Cancer-associated fibroblasts	Secretion of immunosuppressive cytokines: Transforming growth factor beta, IL-6. Extracellular matrix remodeling: Facilitates tumor invasion and forms physical barrier to immune cells. Promotion of regulatory T cell recruitment: Inhibits cytotoxic T cells	Immune evasion: Dampens anti-tumor immune response. Enhanced tumor invasion: Promotes desmoplastic reaction and tissue stiffness. Physical barrier: Limits immune cell infiltration
Tumor-associated macrophages	Predominantly type 2 macrophages phenotype macrophages: Secrete vascular endothelial growth factor and IL-10. Angiogenesis: Promotes new blood vessel formation. Immune suppression: Dampens immune response	Tumor progression: Supports angiogenesis, providing nutrients to tumors. Immune suppression: Contributes to immune evasion and poor prognosis
Endothelial cells	Expression of immune checkpoint molecules: Programmed death-ligand 1, which inhibits T cell function	Tumor-permissive environment: Contributes to immune evasion and progression

IL: Interleukin.