TIM-3

Definition

TIM-3, or T-cell immunoglobulin and mucin-domain containing-3, is an immune checkpoint receptor expressed on various immune cells, including T cells and dendritic cells. It plays a critical role in regulating immune responses, particularly in the context of tumor immune evasion, by inhibiting T cell activation and promoting tolerance to tumors.

5 Must Know Facts For Your Next Test

1. TIM-3 is often upregulated in tumor-infiltrating T cells, which can lead to diminished anti-tumor responses.
2. Binding of TIM-3 to its ligand, galectin-9, leads to T cell exhaustion and promotes a suppressive tumor microenvironment.
3. Blocking TIM-3 has been investigated as a therapeutic strategy in cancer immunotherapy to enhance anti-tumor immunity.
4. In addition to T cells, TIM-3 is also expressed on dendritic cells, where it can influence antigen presentation and T cell priming.
5. The interaction between TIM-3 and galectin-9 is associated with various cancers, including melanoma, lung cancer, and pancreatic cancer.

Review Questions

• How does TIM-3 contribute to the mechanism of tumor immune evasion?
  • TIM-3 contributes to tumor immune evasion by inhibiting T cell activation and promoting T cell exhaustion within the tumor microenvironment. When TIM-3 binds to its ligand galectin-9, it leads to a state of unresponsiveness in T cells, preventing them from effectively attacking tumor cells. This process allows tumors to escape immune surveillance and continue to grow unchallenged.
• Discuss the potential implications of targeting TIM-3 in cancer immunotherapy.
  • Targeting TIM-3 in cancer immunotherapy holds significant promise as it could reverse T cell exhaustion and enhance anti-tumor responses. By blocking TIM-3 interactions with galectin-9, therapies aim to reinvigorate exhausted T cells and restore their ability to recognize and destroy cancer cells. This strategy may be combined with other checkpoint inhibitors like PD-1 to create more effective treatment regimens for patients.
• Evaluate the role of TIM-3 in modulating both anti-tumor immunity and tolerance mechanisms in the context of cancer.
  • TIM-3 plays a dual role in modulating anti-tumor immunity and tolerance mechanisms. On one hand, it acts as a negative regulator of T cell activation, leading to a tolerogenic environment that allows tumors to evade immune detection. On the other hand, this same pathway can contribute to maintaining self-tolerance under normal conditions. Understanding these complexities is crucial for developing effective immunotherapies that can selectively enhance anti-tumor immunity while preserving normal immune function.

Related terms

Immune Checkpoint: Molecules that downregulate the immune system, preventing excessive responses and maintaining self-tolerance, often exploited by tumors to evade immune detection.

T Regulatory Cells (Tregs): A subset of T cells that modulate the immune response, maintaining tolerance to self-antigens and preventing autoimmune disease, which can also facilitate tumor immune evasion.

PD-1: Programmed cell death protein 1 is another immune checkpoint receptor that inhibits T cell function when bound to its ligands, playing a key role in tumor evasion strategies.