Apoptosis ; Burkitt Lymphoma ; Cell Line ; Cell Line, Tumor ; Humans ; Lymphocytes ; Programmed Cell Death 1 Receptor

Cross-priming is an important mechanism to activate immune response, which includes two classical signal pathways. Co-stimulatory signals are essential in the effective activation and B7-family is considered to be one of the most important factor in immunotherapy. PD-L1 is a new member of B7 family, whose ligand is PD-1. PD-1/PD-L1 can down-regulate the activation of immune response, which has become a focus of research. This article reviewed the expression of PD-1/PD-L1 in normal tissue and tumor, focusing on the status of PD-1/PD-L1 pathway study in leukemia, lymphoma, multiple myeloma, aplastic anemia and so on, in order to provide a new way for treatment of hematologic diseases.
B7-H1 Antigen ; metabolism ; Hematologic Diseases ; metabolism ; Humans ; Programmed Cell Death 1 Receptor ; metabolism ; Signal Transduction

Abstract　　Tumor cells avoid immune surveillance by overexpressing ligands of checkpoint receptors on tumor cells or adjacent cells, resulting in inability or exhaustion of T cells. Numerous studies have shown that lymphoma cells highly expressed programmed cell death ligand-1 (PD-L1), suggesting that PD-1 may become an important target for lymphoma treatment. By targeting the PD-1 protein, the cellular activity of T cells will be significantly enhanced, and the tumor growth will be inhibited. Recently, antibodies against PD-1 have shown high efficacy and safety in the clinical studies of lymphoma, which are expected to become the targeted therapeutic drugs for lymphoma. In order to deeply understand the application of PD-1 antibody in treatment of lymphoma, this review briefly summaries the present state of lymphoma studies, the action mechanism and preparation method of PD-1 antibody in clinical treatment of lymphoma.
Antibodies, Monoclonal ; Apoptosis ; B7-H1 Antigen ; Humans ; Lymphoma ; Programmed Cell Death 1 Receptor

Bladder urothelial carcinoma(BUC)is a common malignant tumor in the urinary system.Pt-based chemotherapy has long been a standard therapeutic method for resectable or metastatic BUC,but with poor outcomes.Immune checkpoint inhibitors specific to programmed death 1(PD-1)/programmed death-ligand 1(PD-L1)and cytotoxic T lymphocyte-associated protein 4(CTLA-4)pathways have shown significant antitumor activities,safety,and enduring reactivity in clinical trials,thus creating a new epoch for the treatment of advanced-stage BUC.This article reviews the relationships of BUC with PD-1/PD-L1 and CTLA-4 pathways,as demonstrated in clinical trials.In particular,the authors elucidate the clinical studies on the application of immune checkpoint inhibitors in different BUC stages and their optimal combining strategies,with an attempt to improve the clinical use of immune inhibitors for BUC treatment.
Apoptosis ; B7-H1 Antigen ; CTLA-4 Antigen ; Immunotherapy ; Programmed Cell Death 1 Receptor ; Signal Transduction

OBJECTIVE: To observe the effects of herbal cake separated moxibustion on macrophage effector molecule T-cell immunoglobulin and mucin-domain containing-4 (Tim-4) and ubiquitination of programmed cell death protein 1 (PD-1) in rabbits with immunosuppression, and to explore the possible mechanism on herbal cake separated moxibustion in improving immunosuppression. METHODS: Thirty-two big-ear white rabbits were randomly divided into a normal group, a model group, a moxa stick moxibustion group and a herbal cake separated moxibustion group, 8 rabbits in each group. Except the normal group, the immunosuppression model was established by intraperitoneal injection of cyclophosphamide of60 mg/kg in the other 3 groups. "Shenque" (CV 8), "Shenshu" (BL 23), "Zusanli" (ST 36), etc. were selected in both the moxa stick moxibustion group and the herbal cake separated moxibustion group. Moxa stick moxibustion was applied in the moxa stick moxibustion group, one cone at each acupoint; herbal cake separated moxibustion was applied in the herbal cake separated moxibustion group, 5 cones at each acupoint. The intervention was given once every other day for 10 times in both groups. Leukocyte content in peripheral blood was detected by blood cell analyzer; the positive expression of PD-1 in CD⁺₄ T lymphocytes, CD⁺₈T lymphocytes and CD⁺₆₈ macrophages in peripheral blood was measured by flow cytometry, the serum levels of interleukin 2 (IL-2), CD₈, CD₆₈ and Tim-4 were detected by ELISA, and the expression of Tim-4 and F-box only protein 38 (FBXO38) in the liver and spleen tissues was measured by immunohistochemistry. RESULTS: Compared with the normal group, in the model group, white blood cell count (WBC) and percentage of neutrophils (NEU%) were decreased while percentage of lymphocyte (LYM%) was increased (P<0.01) in peripheral blood; the positive expression rates of PD-1 in CD⁺₄ T lymphocytes, CD⁺₈T lymphocytes and CD⁺₆₈ macrophages in peripheral blood were increased (P<0.01); the serum levels of IL-2, CD₆₈ and Tim-4 were increased (P<0.01), the serum level of CD₈ was decreased (P<0.01); the average optical density (AOD) of Tim-4 in the liver tissue and FBXO38 in the liver and spleen tissues was increased (P<0.01). Compared with the model group, in the moxa stick moxibustion group and the herbal cake separated moxibustion group, WBC and NEU% were increased (P<0.01); the positive expression rates of PD-1 in CD⁺₄ T lymphocytes, CD⁺₈T lymphocytes and CD⁺₆₈ macrophages in peripheral blood were decreased (P<0.01); the serum levels of IL-2, CD₆₈ and Tim-4 were decreased (P<0.01), the serum levels of CD₈ were increased (P<0.01); the AOD of Tim-4 and FBXO38 in the liver tissue and FBXO38 in the spleen tissue was decreased (P<0.01, P<0.05). Compared with the moxa stick moxibustion group, in the herbal cake separated moxibustion group, the positive expression rate of PD-1 in CD⁺₆₈ macrophages in peripheral blood was increased (P<0.05); serum level of Tim-4 was increased (P<0.01); AOD of Tim-4 in the liver tissue was decreased (P<0.05). CONCLUSION Herbal cake separated moxibustion can improve immunosuppression by regulating the expression of macrophage effector molecule Tim-4 and the FBXO38 mediated ubiquitination of PD-1, Tim-4 may be one of the specific indexes of immunomodulation involving with herbal cake separated moxibustion.
Animals ; Rabbits ; Interleukin-2/genetics* ; Moxibustion ; Programmed Cell Death 1 Receptor/genetics* ; Immunosuppression Therapy ; Ubiquitination

Aminopyridines ; Benzamides ; Humans ; Programmed Cell Death 1 Receptor ; Sezary Syndrome/drug therapy* ; Skin Neoplasms/drug therapy*

Transmembrane protein, also known as integral membrane protein, can be distributed in the lipid bilayer or across the entire membrane, and it plays an important role in cell signal transduction. It has been discovered that multiple transmembrane proteins are involved in the regulation of tumor signals. Recent studies have revealed that the abnormal expression of some transmembrane protein is closely related to the occurrence, development and prognosis of non-Hodgkin's lymphoma (NHL), including programmed cell death protein 1 (PD-1), TMEM30A, NOTCH1, TOLL-like receptor (TLR), sphingosine-1-phosphate receptor, TRAIL, etc. The study on these transmembrane proteins and related genes has important clinical significance for the treatment and prognosis of NHL, and it may become a new therapeutic target. At present, there have been some research results in this field at home and abroad. This article reviewed the research progress of transmembrane protein that has inhibitory effects on NHL in recent years.
Humans ; Lipid Bilayers ; Lymphoma, Non-Hodgkin/therapy* ; Prognosis ; Programmed Cell Death 1 Receptor ; Sphingosine-1-Phosphate Receptors

Nivolumab is anti-programmed death 1 (PD1) receptor antibody, which can be used in the treatment of metastatic squamous cell cancer. By blocking the PD1 receptors on T cells, it enhances T-cell response against cancer cells. A 69-year-old man, who works as a farmer, presented with erythematous lichenified plaques on sun-exposed areas, such as the face, the chest, and both the forearms. Before the hospital visit, he was receiving lung cancer treatment with paclitaxel and cisplatin, but there was no improvement. Subsequently, the regimen was changed into nivolumab, and PET-CT showed decreased in cancer size. However, skin rashes developed simultaneously. It is consistent with the results of a previous study in which cutaneous side effects developed in 42% of responders compared to 7% of non-responders. Herein, we report a case of nivolumab-induced cutaneous toxicity on sun-exposed areas based on the clinical findings, including the distribution of rashes, which were improved after decreasing the nivolumab dose with literature review.
Aged ; Cisplatin ; Exanthema ; Farmers ; Forearm ; Humans ; Lung Neoplasms ; Neoplasms, Squamous Cell ; Paclitaxel ; Programmed Cell Death 1 Receptor ; T-Lymphocytes ; Thorax

Abstract　　Acute myeloid leukemia (AML) is a malignant clonal proliferative hematological tumor that originates from hematopoietic stem progenitor cells. Traditional chemotherapy can achieve complete remission in most patients, but so far, only allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only way to cure AML. Recurrence, drug resistance, and transplant-related deaths remain a key issue for AML treatment. Therefore, finding new treatments to improve the prognosis of patients with AML is urgently needed. In recent years, the emergence of new immunotherapy has revolutionized the concept of cancer treatment in the past few decades. Cellular immunotherapy represented by chimeric-antigen receptor T cell (CAR-T) and immunological detection point inhibitor represented by PD-1 blockade have achieved remarkable effects in hematological malignancies. This article mainly reviews the recent research progress of CAR-T and PD-1 blockade in the clinical treatment of AML.
Hematopoietic Stem Cell Transplantation ; Humans ; Immunotherapy, Adoptive ; Leukemia, Myeloid, Acute ; Programmed Cell Death 1 Receptor ; Receptors, Chimeric Antigen

Objective: To observe the changes of PD-1 expression, mRNA level and cytotoxic activity of CD19 CAR-T cells during the culture process of CAR-T cells. Methods: The peripheral blood T cells of 6 lymphoma patients with high expression of PD-1 and 6 healthy volunteers were the source of CAR-T cells. The expression of PD-1 was analyzed by flow cytometry. The mRNA level of PD-1 was analyzed by PCR. The cell proliferation was analyzed by CCK-8 assay. The cytotoxicity was analyzed by LDH assay. Results: ①The transfection efficiency of high PD-1 expression T cells and healthy volunteer T cells were as the same (P>0.05) . ②The cell proliferation capacity of CD19 CAR-T cells from high PD-1 expression T cells or healthy volunteer T cells, with or without PD-1 inhibitor were as the same (P>0.05) . ③The cytotoxicity to lymphoma cells of high PD-1 expression T cells and CAR-T cells were lower than that of these two T cells combined with PD-1 inhibitor and the CAR-T cells from healthy volunteer T cells (P<0.001) . There was no difference of the cytotoxicity between the CAR-T cells from high PD-1 expression T cells combined with PD-1 inhibitor and the CAR-T cells from healthy volunteer (P>0.05) . ④There was no difference of the expression of PD-1 in all CAR-T cell groups during the culture process (P>0.05) . There was no difference of mRNA level of PD-1 in all groups during the culture process (P>0.05) . ⑤The PD-1 expression of CAR-T cells increased by the time of culture after contacting with lymphoma cells (P<0.001) . The PD-1 inhibitors could antagonize this effect. There was no difference of mRNA level of PD-1 in all groups after contacting with lymphoma cells (P>0.05) . Conclusion: The PD-1 expression of CAR-T cells from high PD-1 expression T cells increased by the time of culture after contacting with lymphoma cells. However, the mRNA level of PD-1 of all groups did not change, even if PD-1 inhibitor was applied.
Antigens, CD19 ; Humans ; Programmed Cell Death 1 Receptor/genetics* ; RNA, Messenger ; Receptors, Antigen, T-Cell ; T-Lymphocytes