In-depth Overview of Immune Checkpoint Proteins

Research Areas of Immune Checkpoint Proteins

Immune checkpoint proteins are a class of important proteins that regulate immune responses, and their research fields are extensive. The following are several common immune checkpoint research fields:

1. Immunomodulation: Researchers are committed to in-depth understanding of the function and regulatory mechanism of immune checkpoint proteins, and to explore their role in immune regulation. This includes studies on immune tolerance, immune escape, and immune balance, in order to achieve precise regulation of immune responses by regulating the expression and function of immune checkpoint proteins.
2. Tumor immunotherapy: Immune checkpoint proteins are of great significance in tumor immunotherapy. Researchers are committed to exploring the interaction between tumor cells and immune cells, studying the expression and regulation mechanism of immune checkpoint proteins in tumor cells, and developing antibody drugs targeting immune checkpoint proteins to relieve immune suppression and activate immune responses, Enhance anti-tumor effect.
3. Autoimmune diseases: Abnormal expression and dysfunction of immune checkpoint proteins are closely related to the occurrence and development of autoimmune diseases. Researchers are committed to studying the mechanism of action of immune checkpoint proteins in autoimmune diseases, and finding new targets and strategies for the treatment of autoimmune diseases, so as to achieve the balance of immune regulation and improve the therapeutic effect.
4. Infectious diseases: Immune checkpoint proteins also play an important role in infectious diseases. Researchers are committed to studying the regulatory mechanism of immune checkpoint proteins in the process of infectious diseases, and finding ways to intervene in immune checkpoint proteins to enhance the body's immune response and clearance ability against pathogens.

In general, the research field of immune checkpoint proteins involves many aspects such as immune regulation, tumor immunotherapy, autoimmune diseases and infectious diseases. Through the in-depth study of the function and regulatory mechanism of immune checkpoint proteins, and the search for new therapeutic targets and strategies, it is expected to bring new breakthroughs and hopes for immunotherapy and disease treatment.

Co-inhibitory Receptors: Regulating Immune Responses and Implications in Immunotherapy

Co-inhibitory receptors are proteins within the immune system that exert a negative regulatory effect, participating in the modulation of immune cell activation and antigen response. By binding to their corresponding ligands, these receptors inhibit the activity and function of T cells, preventing excessive immune responses and self-tissue damage.

Notable co-inhibitory receptors include CTLA-4, PD-1, LAG-3, and TIM-3, among others. CTLA-4 competitively inhibits the activation signal of T cells by binding with B7 molecules, playing a negative regulatory role. PD-1 inhibits T cell effector function by interacting with PD-L1 or PD-L2, maintaining immune balance. LAG-3 and TIM-3 also suppress T cell activation and proliferation, exerting negative regulatory effects.

Co-inhibitory receptors play a significant role in immune evasion and immune tolerance. In certain scenarios, tumor cells or infectious pathogens exploit the interaction between co-inhibitory receptors and their ligands to suppress immune cell activity and evade immune attacks. Consequently, strategies aimed at inhibiting co-inhibitory receptors are widely utilized in immunotherapy. By employing antagonists targeting co-inhibitory receptors, such as anti-CTLA-4 and anti-PD-1 antibodies, T cell anti-tumor activity can be restored, bolstering the immune system's ability to combat tumors.

In summary, co-inhibitory receptors play a crucial role in immune response regulation. The investigation of their function and regulatory mechanisms, alongside the development of antibody drugs targeting these receptors, holds great significance in the realms of immunotherapy and disease treatment. These studies contribute to a better understanding of immune regulation mechanisms, the formulation of novel therapeutic strategies, enhanced treatment efficacy, and renewed hope for the management of immune diseases and cancer.

CTLA-4

CTLA-4 (cytotoxic T lymphocyte-associated antigen-4) is a co-inhibitory receptor widely expressed on the surface of T cells. It plays an important role in immune regulation. CTLA-4 plays a negative regulatory role by binding to co-stimulatory molecules B7-1 (CD80) and B7-2 (CD86) and competitively inhibiting the activation signal of T cells.

CTLA-4 has multiple mechanisms of action in regulating the immune response of T cells. First, CTLA-4 can reduce the activity and proliferation of T cells and inhibit the production of cytokines. Secondly, CTLA-4 can prevent B7-1 and B7-2 from binding to the stimulating receptor CD28, thereby blocking the transduction of CD28 signal and inhibiting the activation of T cells. Finally, CTLA-4 can also induce the generation and function enhancement of anti-inflammatory regulatory T cells (Treg), which further suppresses the immune response.

CTLA-4 is of great significance in the field of immunotherapy. By using anti-CTLA-4 antibody, the negative regulatory effect of CTLA-4 can be inhibited, the inhibition of T cells can be relieved, and the anti-tumor immune response can be enhanced. Anti-CTLA-4 antibody has been widely used in the treatment of malignant tumors, and achieved remarkable clinical efficacy.

PD-1

PD-1 (Programmed Cell Death Protein 1) is an immune checkpoint protein widely expressed on the surface of T cells, B cells and other immune cells. It plays an important role in regulating the immune response. PD-1 plays a negative regulatory role by binding to its ligand PD-L1 (Programmed Death-Ligand 1) or PD-L2, and inhibits the activity and function of T cells.

The main function of PD-1 is to suppress excessive immune response and maintain immune balance. When PD-1 binds to its ligand, it will inhibit the proliferation, cytokine production and killing ability of T cells, thereby reducing the attack of immune cells on their own tissues. This regulatory mechanism plays an important role in immune tolerance, autoimmune diseases, and tumor immune escape.

However, some tumor cells highly express PD-L1, which binds to PD-1 on T cells and escapes immune attack in this way. This presents an opportunity to utilize anti-PD-1 antibody or anti-PD-L1 antibody as an immunotherapeutic strategy. By inhibiting the interaction between PD-1 and PD-L1, the inhibition of T cells can be relieved and the anti-tumor immune response can be enhanced, thereby significantly improving the prognosis of tumor patients.

Co-stimulatory Receptors: Enhancing Immune Responses and Implications in Immunotherapy

Co-stimulatory receptors play a vital role in the activation and regulation of immune responses. These proteins, found in the immune system, bind to costimulatory ligands to enhance T cell activity and function by providing stimulatory signals.

Among the well-known co-stimulatory receptors are CD28 and CD137 (4-1BB). CD28, located on the surface of T cells, interacts with co-stimulatory molecules B7-1 (CD80) and B7-2 (CD86) to deliver a powerful stimulating signal. This signal promotes the activation, proliferation, and cytokine production of T cells. CD137, primarily expressed on activated T cells, binds to its ligand CD137L, initiating signal transduction pathways that enhance T cell viability and function.

Understanding the function of co-stimulatory receptors holds significant implications in immunotherapy. By leveraging the activation signals of these receptors, immune cells' anti-tumor activity and pathogen-fighting capabilities can be enhanced. For instance, utilizing antibodies targeting anti-CD28 or anti-CD137 can amplify T cell activation and proliferation, bolstering the anti-tumor effect of immune cells. Furthermore, co-stimulatory receptors are implicated in immune-related diseases such as transplant rejection, autoimmune diseases, and infections.

Studying the function and regulatory mechanisms of co-stimulatory receptors, as well as developing activators or antibody drugs that target these receptors, holds immense value in the fields of immunotherapy and disease treatment. These endeavors contribute to a deeper understanding of immune regulation mechanisms, facilitate the development of new immunotherapy strategies, improve therapeutic outcomes, and provide new hope for treating immune-related diseases.

CD28

CD28 is a co-stimulatory receptor widely expressed on the surface of T cells and plays an important role in the activation and regulation of immune responses. CD28 binds to co-stimulatory molecules B7-1 (CD80) and B7-2 (CD86), providing stimulating signals and promoting the activation and proliferation of T cells. CD28 activates the expression of various cytokine genes, such as IL-2 and IFN-γ, through its intracellular signal transduction pathway, thereby enhancing the immune function of T cells. Activation signals of CD28 work together with T cell receptor signaling to enhance the potency of the immune response through synergistic effects.

CD28 is of great significance in the field of immunotherapy. By using anti-CD28 antibodies or using co-stimulatory signal enhancers, the activation and function of T cells can be enhanced to promote tumor-specific immune responses and inhibit tumor growth and spread. In addition, CD28 is also involved in the occurrence and development of immune-related diseases such as autoimmune diseases, infection and transplant rejection.

In-depth study of the function and regulatory mechanism of CD28, and the development of CD28-specific activators or antibody drugs are of great significance for immunotherapy and disease treatment.

CD137

CD137 (4-1BB) is a co-stimulatory receptor mainly expressed on the surface of activated immune cells such as T cells, B cells and natural killer cells. It binds to its ligand CD137L, activates immune cells through signaling pathways, and enhances their viability and function.

The activation signal of CD137 can promote the proliferation and survival of T cells, enhance the killing activity of cytotoxic T cells (CTL), and promote the formation of memory T cells. In addition, CD137 can also activate B cells and increase antibody production. The activation signal of CD137 can also induce the production of cytokines, such as IL-2, IL-6 and IFN-γ, to further promote the activity of immune cells.

Due to its important role in immune regulation, CD137 has become a research hotspot in immunotherapy. By using anti-CD137 antibodies or using CD137 agonists, the anti-tumor activity and anti-pathogen ability of immune cells can be enhanced. The application of CD137 agonists has achieved some success in laboratory and clinical trials, showing its potential in tumor immunotherapy.

Reference

[1] Catakovic K, Klieser E, Neureiter D, Geisberger R. T cell exhaustion: from pathophysiological basics to tumor immunotherapy. Cell Commun Signal. 2017;15(1):1. Published 2017 Jan 5. doi:10.1186/s12964-016-0160-z https://pubmed.ncbi.nlm.nih.gov/28073373/

[2] Schnell A, Bod L, Madi A, Kuchroo VK. The yin and yang of co-inhibitory receptors: toward anti-tumor immunity without autoimmunity [published correction appears in Cell Res. 2020 Feb 21;:]. Cell Res. 2020;30(4):285-299. doi:10.1038/s41422-020-0277-x https://pubmed.ncbi.nlm.nih.gov/31974523/