negative regulation of T cell mediated immune response to tumor cell

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate, or extent of a T cell mediated immune response to tumor cell. [GOC:add]

Negative regulation of T cell mediated immune response to tumor cells is a complex process involving multiple mechanisms that suppress the activity of T lymphocytes (T cells) against cancer cells. This suppression is crucial for maintaining immune homeostasis and preventing autoimmunity, but it can also allow tumor cells to escape immune surveillance and grow.

One key mechanism involves **immune checkpoints**, which are molecules expressed on immune cells that regulate their activation and function. These checkpoints include CTLA-4, PD-1, and TIM-3, among others. When these checkpoints are engaged by their ligands on tumor cells, they send inhibitory signals to T cells, suppressing their activity. This suppression can lead to **T cell exhaustion**, a state where T cells become unresponsive to tumor antigens and lose their ability to kill cancer cells.

**Tumor-associated macrophages (TAMs)** also play a role in suppressing T cell responses. These macrophages are recruited to the tumor microenvironment and often exhibit an immunosuppressive phenotype. They can produce immunosuppressive cytokines like IL-10 and TGF-β, which inhibit T cell activation and function. TAMs can also express molecules like PD-L1, which can bind to PD-1 on T cells and deliver inhibitory signals.

**Tumor cells themselves** can also evade immune responses by expressing immunosuppressive molecules or by creating an immunosuppressive microenvironment. For example, some tumors can express FasL, a molecule that induces apoptosis in T cells, or they can produce immunosuppressive cytokines like IL-10 or TGF-β. They can also create a hypoxic microenvironment, which inhibits T cell function and promotes tumor growth.

**Regulatory T cells (Tregs)** are a specialized type of T cell that plays a crucial role in suppressing immune responses, including those against tumors. Tregs express high levels of the transcription factor Foxp3, which is essential for their development and function. They suppress T cell responses by producing immunosuppressive cytokines like IL-10 and TGF-β, and by directly interacting with T cells to inhibit their activation.

**Other mechanisms** involved in negative regulation of T cell mediated immune response to tumor cells include:

- **Apoptosis of T cells**: Tumor cells can induce apoptosis of T cells through various mechanisms, such as expressing FasL or releasing cytotoxic substances.
- **Suppression of T cell differentiation**: Tumor cells can suppress the differentiation of naive T cells into effector T cells, reducing the number of T cells capable of attacking cancer cells.
- **Induction of tolerance**: Tumor cells can induce tolerance in T cells, preventing them from recognizing and attacking tumor antigens.

**Overall, negative regulation of T cell mediated immune response to tumor cells is a complex and multi-faceted process.** Understanding these mechanisms is crucial for developing effective cancer immunotherapies that can overcome tumor immune evasion and stimulate robust antitumor immunity.'
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Proteins (3)

Compounds (40)