The immune components of the tumor microenvironment (TME) play a significant role in either promoting or inhibiting tumor growth. The interaction between tumor cells and immune cells within the TME is complex and can lead to immune suppression, immune evasion, or, conversely, effective immune-mediated tumor destruction.

Targeting the immune components of the TME has become a major focus in cancer therapy. Strategies such as immune checkpoint inhibitors (e.g., anti-PD1, anti-CTLA4), CART cell therapy, and vaccines aim to reawaken the immune system to recognize and destroy tumor cells. Additionally, modulating the activity of TAMs, MDSCs, and Tregs is being explored to overcome the immunosuppressive TME and improve the effectiveness of immunotherapies.

In this Research Topic, we aim to explore either of the following themes:

1. Key Immune Components in the Tumor Microenvironment
1.1. Tumor-Associated Macrophages (TAMs): TAMs (M1) are often polarized towards the M2 phenotype in tumors, where they facilitate tumor progression by secreting growth factors, cytokines, and proteases that support tumor growth, metastasis, and immune suppression.
1.2. M1 Macrophages: Typically have anti-tumor activity by promoting inflammation and stimulating an immune response.
1.3. M2 Macrophages: Promote tumor growth by supporting tissue remodeling, angiogenesis, and suppressing the immune response.

2. Lymphocytes
2.1. Cytotoxic T Cells (CTLs): Recognize and kill tumor cells presenting specific antigens via MHC class I molecules. However, their activity can be suppressed by various TME factors, leading to immune evasion.
2.2. Helper T Cells (Th): Th1 cells support anti-tumor immunity by activating CTLs and macrophages, while Th2 cells can contribute to immunosuppression and tumor progression.
2.3. Natural Killer (NK) Cells: NK cells can recognize and kill tumor cells without the need for prior antigen exposure. However, their activity can be inhibited by the immunosuppressive environment within the TME, reducing their effectiveness in targeting tumor cells.
2.4. Regulatory T Cells (Tregs): Suppress the activity of other immune cells, including CTLs and helper T cells, to maintain immune tolerance. In tumors, Tregs often accumulate and inhibit anti-tumor immunity, allowing tumor cells to evade the immune system.
2.5. B Cells: B cells can produce antibodies against tumor antigens, but they also can play a dual role. In some cases, they promote anti-tumor immunity, while in others, they can contribute to immune suppression and tumor progression through the production of regulatory cytokines.
2.6. Cytokines and Chemokines: The TME contains a complex network of cytokines and chemokines that regulate the recruitment, differentiation, and function of immune cells. Pro-inflammatory cytokines like IFNγ, IL12 typically support anti-tumor immunity. Immunosuppressive cytokines like IL10, TGFβ are often upregulated in the TME and contribute to immune evasion by inhibiting the function of CTLs and NK cells and promoting Treg expansion.

3. Immune Evasion Mechanisms
3.1. Immune Checkpoints: Tumor cells often exploit immune checkpoint molecules like PD1/PDL1 and CTLA4 to inhibit T cell activation and avoid destruction.
3.2. Metabolic Reprogramming: Tumor cells and immune cells in the TME undergo metabolic changes that can lead to the depletion of essential nutrients like glucose and oxygen, further suppressing the function of effector immune cells.
3.3. Immunosuppressive Metabolites: The TME can contain high levels of immunosuppressive metabolites such as adenosine, which inhibit T cell and NK cell activity.

Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.

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Tumor-Associated Macrophages and Tumor-Infiltrating Lymphocytes in the Tumor Microenvironment