Professor Ping's team has issued two articles reporting on new advances in the study of PD-1H immunosuppressive pathways.

In recent years, enzyme immunotherapy for cancer has become a hot field, especially based on blocking the PD-1 / PD-L1 immunosuppressive pathway, which brings good news to many advanced cancer patients.at present, more than ten cancer indications have been approved for this pathway inhibitor, which has completely changed the traditional pattern of cancer treatment.Professor Chen Liping of Yale University is a pioneer in tumor immunotherapy. As early as the late 1990s, his team took the lead in discovering PD-L1 molecules and found that PD-L1 molecules are widely expressed in human tumor tissues.a series of original research work laid the foundation for the success of clinical trials.in addition to the PD-1 / PD-L1 pathway, Professor Chen Liping's team has also identified many new immunosuppressive pathways, among which pd-1h (PD-1 homologue, also known as Vista) is one of them.their early research found that pd-1h molecule is expressed on the surface of T lymphocytes and myeloid cells, which can not only act as a ligand to inhibit T cell activation, but also as a receptor on T cells to receive inhibitory signals [1].Professor Chen Liping's research team published an article in Science Translational Medicine on December 11, 2019, which reported the new function of pd-1h molecule: pd-1h (Vista) - mediated suppression of autoimmunity in systemic and cubaneous lupus erythematosus.different from the previous studies on tumor immunity, this paper expounds that the impairment of pd-1h immunosuppressive pathway may induce an autoimmune disease, lupus erythematosus.on January 9, 2020, the team of Chen Lieping and Professor Xiong Yong of Yale University published the latest article on PNAs: structural insight into T cell coalescence by pd-1h (Vista), which reported the crystal structure of pd-1h molecule and the important structural domains that affect the function of pd-1h.lupus erythematosus is a complex autoimmune disease.there are two kinds of common lupus erythematosus. One is discoid lupus erythematosus (DLE), which mainly affects the skin, and the patient will have butterfly shaped erythematosus on the face; the other is systemic lupus erythematosus (SLE), which affects other tissues and organs in addition to skin tissue, and in severe cases, heart, lung, kidney and other organs will be damaged and life-threatening.because the pathogenesis of this disease has not been clearly studied, the treatment of lupus erythematosus is very limited.in the past 60 years, only one drug has been approved for SLE (anti BAFF) in the world, while dle has not been approved.in STM, the team found that pd-1h deficient mice spontaneously developed lupus like skin inflammation, and increased levels of anti nuclear antibodies, which are characteristic of lupus erythematosus, can be detected in their serum.pd-1h deficient mice were also more sensitive to pristane induced autoimmune diseases.the researchers also detected that pd-1h was highly expressed in skin tissues of MRL / lpr mice and dle patients with spontaneous lupus erythematosus compared with healthy controls.pd-1h deficient BALB / c mice had spontaneous lupus erythematosus dermatitis, and the serum produced antinuclear antibodies.to verify whether pd-1h can be used as a target for the treatment of lupus erythematosus, the researchers injected pd-1h agonist antibody into mice with lupus erythematosus.this antibody is opposite to the antagonistic antibody of inhibitory pathway used in tumor immunotherapy. The antagonistic antibody can block the binding of inhibitory pathway ligand receptor, so as to enhance the body's immune response against tumor, and the excitatory antibody can directly activate the inhibitory receptor and inhibit the immune response.after using pd-1h agonist mAb, the onset time of mice was delayed and the skin diseases were alleviated.in addition, the expansion of inflammatory cytokines, chemokines and immune cells was significantly reduced, indicating that the immune system was less aggressive to its own tissues.the skin tissue of DLE patients was highly expressed pd-1h protein. Pd-1h activated monoclonal antibody delayed the onset of lupus erythematosus mice and alleviated skin symptoms. In the PNAs study, Professor Chen Liping's team cooperated with Professor Xiong Yong's team to analyze the crystal structure of the extracellular domain of human pd-1h protein (resolution of 1.9 A), and focused on the contribution of pd-1h molecular characteristic structure to its function.they found that pd-1h has some characteristic structures which are rarely found in other immunoglobulin family molecules, such as multiple histidine clusters on the surface and extra folding chain and "clamp" structure at the end of extracellular domain, which may play an important role in the inhibition of T cell activation by pd-1h.this study may have important guiding significance for drug development targeting pd-1h inhibitory pathway in the future.pd-1h structure diagram, the blue part indicates the histidine cluster on the molecular surface.in conclusion, Professor Chen Liping's team demonstrated the key regulatory role of pd-1h (Vista) pathway in autoimmune diseases through functional mechanism research, and structural analysis provided potential drug development targets in the later stage.it is reported that Dr. Han Xue and Dr. Vesely of Yale University are the co authors of STM articles; Dr. slator and Dr. Han Xue are the co authors of PNAs articles.original link: plate maker: Ke ref. 1. Coinhibitory receiver pd-1h? Preferentially suppresses CD4 + T cell mediated immunity. Flies dB, Han x, Higuchi T, Zheng L, sun J, ye JJ, Chen L. J, Clin invest. 2014 may; 124 (5): 1966-75