Immune checkpoints: new hope for cancer treatment

Immune checkpoints: new hope for cancer treatment

Immune checkpoints play a vital role in the human immune system. They are a class of proteins on immune cells that can regulate the activity of immune cells and maintain the balance of the immune system. Under normal circumstances, immune checkpoints can prevent immune cells from attacking normal cells and avoid the occurrence of autoimmune diseases. However, cancer cells can use these immune checkpoints to escape the attack of the immune system, leading to the growth and spread of tumors.

Classification of immune checkpoints

Immune checkpoints are mainly divided into two categories: co-stimulatory immune checkpoints and co-inhibitory immune checkpoints.

Co-stimulatory immune checkpoints: This type of immune checkpoint can stimulate the immune process and enhance the immune response. For example, CD28, ICOS, CD137, etc., they act as "accelerators" during T cell activation. These molecules provide co-stimulatory signals by binding to corresponding ligands, promoting T cell proliferation and cytokine secretion.

Co-inhibitory immune checkpoints: In contrast to co-stimulatory immune checkpoints, co-inhibitory immune checkpoints can inhibit the immune process and act as "brakes". Common co-inhibitory immune checkpoints include PD1, CTLA-4, VISTA, etc. These molecules transmit inhibitory signals by binding to ligands, weaken the activity of T cells, and prevent excessive immune response.

Application of immune checkpoints in cancer treatment

Immune checkpoint inhibitors

Immune checkpoint inhibitors are a major breakthrough in cancer treatment. This type of drug enhances the body's immunity to cancer by inhibiting the co-inhibitory immune checkpoint pathway. For example, PD1/PDCD1/CD279 is a T cell surface protein that produces inhibitory activity when it encounters PD-L1/B7-H1/CD274. Some cancer cells express increased PD-L1/B7-H1/CD274, which interacts with PD1/PDCD1/CD279 to escape the attack of T cells. Therefore, immune checkpoint blockade using PD1/PDCD1/CD279 and PD-L1/B7-H1/CD274 blocking antibodies can effectively activate the immune system's attack on cancer cells.

At present, immune checkpoint inhibitors have become an important means of treating many cancers. For example, immune checkpoint inhibitors have achieved remarkable therapeutic effects in the treatment of melanoma. In addition, they have also shown potential in the treatment of various cancers such as renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), urothelial carcinoma, head and neck cancer, ovarian cancer, etc.

Immune checkpoint agonists

In addition to inhibiting co-inhibitory immune checkpoints, activating co-stimulatory immune checkpoints is also a strategy to enhance immune response. For example, agonists of OX40 and 4-1BB have shown certain effects in preclinical studies. However, the use of agonist antibodies needs to be cautious because they may induce serious immune-related adverse events.

Future directions of immune checkpoint research

Combination therapy strategies

In the future, immune checkpoint inhibitors will be used in combination with other treatments to improve the therapeutic effect. For example, combined chemotherapy, anti-vascular targeted therapy, other targeted therapies, etc. These combined treatment strategies can enhance immune response through various mechanisms, such as reducing tumor volume and reducing the release of immunosuppressive substances through chemotherapy; improving tumor vasculature and promoting T cell infiltration through anti-angiogenic drugs.

In short, immune checkpoints have great potential in cancer treatment. Through continuous exploration and innovation, more effective immunotherapy options are expected to be developed in the future, bringing more hope to cancer patients.