Important research results focus on new achievements made by scientists in the study of PD-1 therapy!

this article, the small editor compiled a number of important research results, jointly focus on scientists in the PD-1 therapy research results, share to everyone!
Picture Source: Nature.
Nature: Revealing that ILC2 cells enhance the efficacy of anti-PD-1 immunotherapydoi: 10.1038/s41586-020-2015-4 congenital lymphocytes (in lymphumcellsoid, ILC), also known as solid immune cells, are a class of lymphatic groups that are different from T-cells and B cells, and are located on the surface of the intestinal membrane. They lack cloned antigen receptors and do not undergo the rearrangement process of the Rag gene during differentiation. Within hours of infection, ILC is able to activate to have a protective effect. Depending on the cytokine expression spectrum, ILCcani can be divided into three groups: ILC1, ILC2 and ILC3, where ILC1 is similar to Th1, which mainly expresses IFN-g, which is mainly targeted at intracellular bacterial and parasitic infections; Similar to Th2, cell factors such as IL-5 and IL-13 are expressed to effectively protect against parasitic infections and allergic reactions, and ILC3 expresses IL-17A and IL-22, which are involved in the
bacteria
infection response sourcing in the intestines. Once exposed to harmful stress, they produce a large number of cytokine effectors. These ILcs play a vital role in regulating immune responses of type I, Type 2 and Type 3 (or Th17 cells), which control the host's protective immune response and intestinal stability. . ILC2 regulates inflammation and immunity in mammalian tissues. Although ILC2 has been found in these tissues for cancer, their role in anti-cancer immune response and immunotherapy is unclear. In a new study, researchers from research institutions such as memorial Sloan Kettering Cancer Center in the United States found that ILC2 is immersed in pancreatic catheter adenocarcinoma (PDAC) to activate tissue-specific antitumor immune responses. Interleukin-33 (IL33) activates tumor ILC2 and CD8 plus T cells in in situ pancreatic tumors in mice, but does not activate tumor ILC2 and CD8 plus T cells in mouse allogeneic skin tumors, thereby inhibiting the growth of pancreatic-specific
tumor
growth, the results of which were recently published in the journal Nature.2(
Science: Blocking EGFR to improve the efficacy of anti-PD-1 drugs against EGFR mutation lung adenocarcinoma doi: 10.1126/sciimmunol.aav3937is one of the leading causes of cancer-related deaths in lung cancer worldwide. Approximately 80% of lung cancer cases are classified as non-small cell lung cancer (NSCLC). Several changes in the cancer-causing driving gene have been reported in NSCLC, including the epidermal growth factor receptor (EGFR) coding gene and the mesomutated lymphoma kinase (ALK) coding gene. In a new study, researchers from Japan's National Cancer Center and Nagoya University and other research institutions studied the immune phenotype of
eGFR mutant lung adenocarcinoma
microenvironment (TME), in which the anti-PD-1
monoantinos
is treatment was largely ineffective in the case of EGFR mutant lung adenocadenoma, which is largely ineffective.however, EGFR mutant lung adenocarcinoma has an inflamed immunosuppressive tumor microenvironment, where CD4-effect regulating T cells (CD4 plus effect sregulatory T cell) usually exist in the inflamed
tumor
microenvironment. EGFR signal activates JNK (cJun N-terminal kinase, cJun N end kinase) / cJUN and reduces interferon regulatory factor-1 (IRF1): the former increases CCL22 to recruit CD4 plus regulatory T cells;
Nature: Pre-inhibition of TNF significantly enhances the efficacy of PD-1 and CTLA-4 combination immunotherapy and reduces side effects doi: 10.1038/s41586-019-1162-y a collaborative experimental study led by researchers from Cima and Navarra Clinical University proposed a new approach to cancer treatment, i.e. the use of joint immunotherapy to address toxicity and efficacy in animal models. This clinical strategy involves blocking a protein that is involved in immune system regulation (called
tumor
necrosis factor, TNF), and combined immunotherapy (a protein that inhibits other "slowing" immune responses such as PD-1 and CTLA-4). The results of the study were published recently in Natrue.in this study, we found that the immune regulation function of tumor necrosis factors is optional and even harmful to this combination immunotherapy to some extent. We have demonstrated in these animal models that preventive blocking of TNF prior to immunotherapy can avoid
adverse reactions
and improve treatment response. This allows us to better adjust the dose of the drug to achieve a stronger anti-
tumor
effect. Because in terms of prevention, it means we can use the methods we've used in our daily practice to treat
autoimmune
adverse reactions
, the researchers said. Experts point out that the next step is to move the study to clinical. Dr Melero said: "If we get the results of this study in patients, it will change the way cancer is treated. However, despite these promising results in animal models, we must be very careful with their interpretation, as we are not sure whether they will be replicated in patients
on going on
clinical trials, or in patients who are about to start treatment.4:
Nat Med: An anti-PD-1 treatment can predict the prognosis of melanoma patients! doi: 10.1038/s41591-019-0357-ythe immune response of patients to PD-1
treatment simply after treatment, and reactive T lymphocytes can be detected in the blood after 3 weeks. But the researchers don't know whether this early blood-based test represents changes in the microenvironment

tumors. To this end, researchers from the University of Pennsylvania and other units conducted a new
clinical trial of stage III/IV
melanoma
patients
and found that an auxiliary anti-PD-1 treatment prior to surgery could predict the clinical outcomes of surgically removable
melanoma
patients, published recently in Nature Medicine.before the experiment began, the researchers speculated that the recovery of the immune system in the tumor tissue should be detected three weeks after anti-PD-1 treatment, so this response would be associated with disease-free survival. The researchers treated 27 patients with anti-PD-1 treatment before surgery, and all of them detected a rapid, strong anti-tumor response, with eight of them experiencing even a full or primary pathological response, all of which were in a state of
-free tumor
.
Cancer Res: Joint target miR-146a and PD-1 enhance anti-tumor immunoastic effective treatment of melanoma doi: 10.1158/0008-5472.CAN-1397 micro
RNA is a small
non-coding RNA expression in the cell, can regulate the level of expression of genes after transcription, and immune response in a variety of types of cancer. Recently, researchers from the University of Freiburg Medical Center in Germany discovered a microRNA that inhibits the immune response of anti-
tumors
in a microenvironment

melanoma, and suggested new strategies for treating
melanoma
. The findings were published in the international academic journal Cancer Research.in the study, researchers found that miR-146a acts as an immuno-active negative regulatory factor. Studies showed increased expression levels in the microenvironment tissue of melanoma, with miR-146a knockout mice surviving longer and having fewer metastatic lesions than wild
melanoma
mice forming a lotus tumor.
Picture Source: Wikipedia/CC BY-SA 3.0. 6.
Science Sub-journal: Revealing the side effects of immunocheckpoint blocking therapy! Anti-PD-1 treatment severs the analgesic effects of opioids doi: 10.1126/scitranslmed.aaw6471 immunocheckpoint blocking therapy using PD-1 targeted antibodies has shown encouraging results in treating a wide range of
tumor
sorceries. Opioid therapy is commonly used in cancer patients to control disease-related pain, such as morphine, which produces analgesic effects through the opioid receptor (MOR). However, the PD-1 signalinnisofe in neurons is largely unknown. There have been recent reports of primary sensory neurons expressing PD-1, the activation of PD-1, which inhibits neuronal excitability and pain. In a new study, researchers from research institutions such as Duke University Medical Center in the United States reported that morphine analgesics and MOR signal transduction require neuronal PD-1. The findings are published in the journal Science Translational Medicine.the analgesic effects it caused were destroyed in Pd1 knockout mice, whole body or intrauterine injection of morphine. Morphine also had ananalgesic effect in wild mice after intravenous or intrauterine injections of navuzumadrin, a clinically used anti-PD-1 monoclonal antibody. In mouse models of inflammatory, neurological and cancerous pain, the analgesic effect of spinal morphine was destroyed after their PD-1 was knocked out. MOR and PD-1 are expressed in sensory neurons and their axons in mouse and human DRG tissues.
Nat Commun: Blocking Siah2 enhances the anti-tumor immune response of PD-1 inhibitors doi: 10.1038/s41467-019-13826-7 In a new study, researchers from the Sanford-Burnham-Priebes Medical Discovery Institute and the University of New York School of Medicine have discovered a new way to improve the immune system's ability to fight cancer. They used mouse models to identify the siah2 protein playing an important role in controlling an immune cell called a class of regulated Treg, which limits the effectiveness of the immunotherapy currently in use, according to a recent study published in the journal Nature Communications.researchers said that while Siah2 was involved in controlling events that regulate cancer production, the study provided the first direct evidence of its role in the immune system's anti-tumor immune response. Our study shows that in mice lacking the Siah2 gene, PD-1 inhibitors can be used to treat
tumor
that are not currently responsive to the therapy, thus providing a means to expand the effectiveness of immunotherapy. These findings also provide further reasons for our efforts to find a drug that blocks Siah2.8
Science Sub-Journal: Challenge the Routine! Professor Tinpin found that activating PD-1H is promising to treat lupus doi:10.1126/scitranslmed.aax1159 Over the past decade, scientists have found that key regulators that block the immune system help activate the body's natural defenseagain against multiple forms of cancer, opening a new era in cancer immunotherapy. For example, immunocheckpoint blocking drugs (also known as immunocheckpoint inhibitors) can effectively treat many cancers by blocking the immune checkpoint PD-1 or CTLA-4 on the surface of T cells. now, in a new study from Yale University in the United States, researchers essentially reversed that view by genetically knocking out BALB/c mice that lacked the immunosuppressive receptor PD-1H (also known as VISTA or B7-H5) and found that these PD-1H knockout mice produce systemic
autoimmune
diseases and skin
autoimmune
diseases similar to those of human slupus --- the two forms of lupus and skin lupus ---, and are more susceptible to the effects of proimmune immunity induced by the propane." In systemic lupus, the immune system attacks multiple organs, and the typical feature of skin-type lupus is significant skin malformations, the findings were recently published in the journal Science Translational Medicine. these findings suggest that impaired PD-1H function can cause damaging immune system attacks on the skin and organs, a typical feature of the autoimmune disease lupus. Besides, this.