The morbidity and mortality of lung cancer is the first in the world, immunotherapy has become a important treatment strategy in addition to chemotherapy, radiotherapy and targeted therapy. In recent years, the US Food and Drug Administration (FDA) has successively approved immunological checkpoint inhibitors as standard programs for non-small cell lung cancer (NSCLC) in second-line or first-line treatment. The National Comprehensive Cancer Network (NCCN) also recommends immunological checkpoint inhibitors as the standard treatment for small cell lung cancer (SCLC). Now, the treatment for lung cancer has entered the era of precision treatment, it is very important to select effective and reliable biomarker for the dominant populations of lung cancer to receive immunotherapy. A large number of researchs indicated that tumor mutation burden (TMB) may be an independent predicted biomarker for immunotherapy, but with limitations. This article reviewed the predictive value of TMB and its limitations in the field of immunotherapy for lung cancer.
Animals ; Biomarkers ; metabolism ; Humans ; Immunologic Factors ; administration & dosage ; Immunotherapy ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; Mutation ; Tumor Burden

Predicting treatment responses in advanced prostate cancer (PCa) currently centres on prostate-specific antigen (PSA) kinetics and on being able to visualize measurable changes in imaging modalities. New molecular markers have emerged as potential diagnostic and prognostic indicators; these were summarized in Part I of this review in the Asian Journal of Andrology. A number of molecular markers are now being used to enhance PCa imaging and staging. However, management options for advanced and hormone-resistant PCa (HRPC) are limited and additional therapeutic options are needed. Molecular markers have been proposed as potential therapeutic targets using gene therapy and immunomodulation. Additionally, markers identified in early PCa and precursor lesions may offer novel targets for chemoprevention and vaccine development. This review summarizes the current advances regarding the roles of these markers in the management of PCa.
Antineoplastic Agents ; therapeutic use ; Biomarkers, Tumor ; genetics ; metabolism ; Cancer Vaccines ; therapeutic use ; Genetic Therapy ; Humans ; Immunologic Factors ; therapeutic use ; Male ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; metabolism ; therapy

Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin super-family receptor ILT2 (synonyms: LIR1, MIR7, CD85j), we have selected a range of mutants with binding affinities enhanced by up to 168,000-fold towards the conserved region of major histocompatibility complex (MHC) class I molecules. Produced in a dimeric form, either by chemical cross-linking with bivalent polyethylene glycol (PEG) derivatives or as a genetic fusion with human IgG Fc-fragment, the mutants exhibited a further increase in ligand-binding strength due to the avidity effect, with resident half-times (t(1/2)) on the surface of MHC I-positive cells of many hours. The novel compounds antagonized the interaction of CD8 co-receptor with MHC I in vitro without affecting the peptide-specific binding of T-cell receptors (TCRs). In both cytokine-release assays and cell-killing experiments the engineered receptors inhibited the activation of CD8(+) cytotoxic T lymphocytes (CTLs) in the presence of their target cells, with subnanomolar potency and in a dose-dependent manner. As a selective inhibitor of CD8(+) CTL responses, the engineered high affinity ILT2 receptor presents a new tool for studying the activation mechanism of different subsets of CTLs and could have potential for the development of novel autoimmunity therapies.
Amino Acid Sequence ; Antigens, CD ; chemistry ; genetics ; pharmacology ; Autoimmunity ; Biological Assay ; Cell Line ; Cytotoxicity, Immunologic ; genetics ; immunology ; Dose-Response Relationship, Immunologic ; Humans ; Immunoglobulins ; immunology ; metabolism ; Immunologic Factors ; chemistry ; genetics ; pharmacology ; Kinetics ; Leukocyte Immunoglobulin-like Receptor B1 ; Lymphocyte Activation ; genetics ; immunology ; Major Histocompatibility Complex ; genetics ; immunology ; Molecular Sequence Data ; Molecular Targeted Therapy ; Mutagenesis, Site-Directed ; Peptide Library ; Polyethylene Glycols ; Protein Binding ; genetics ; immunology ; Receptors, Immunologic ; chemistry ; genetics ; Recombinant Fusion Proteins ; genetics ; metabolism ; T-Lymphocytes, Cytotoxic ; immunology ; metabolism

LZ-8 protein, isolated from a well known Chinese traditional medicinal fungus Ganoderma lucidum, is the first member of fungal immunomodulatory protein, members of which have been isolated from a variety of medicinal and edible mushrooms in the last two decades. The protein plays a multifunctional and important role in modulating immune system. In this report, in order to get LZ-8 protein crystals, the LZ-8 gene was expressed and purified by affinity chromatography, gel filtration chromatography and anion exchange chromatography subsequently. The protein was then crystallized using the hanging-drop vapour-diffusion method. The LZ-8 crystals were obtained and the phase information was calculated by X-ray diffraction. The resolution of LZ-8 crystals is 3.2A. This study will provide an insight into the structure of fungal immunomodulatory proteins.
Animals ; Crystallography ; Fungal Proteins ; biosynthesis ; genetics ; immunology ; Ganoderma ; genetics ; metabolism ; Genetic Vectors ; genetics ; Immunologic Factors ; biosynthesis ; genetics ; Mice ; Recombinant Proteins ; biosynthesis ; genetics ; immunology

OBJECTIVETo investigate the efficacy of IFN-alpha on severe acute pancreatitis (SAP) of IFN-alpha.

METHODSA SAP model was developed in adult male rats by retrograde injection of 5% sodium taurocholate in the pancreatic duct. Serum amylase was measured by the blue-starch method and serum cytokines were determined by ELISA.

RESULTSCompared with to the control group, less pancreatic injury and lower amylase level were observed treat in the rats with IFN-alpha. In contrast, the concentration of IL-10 was higher.

CONCLUSIONIFN-alpha has significant curative effect on SAP.

Animals ; Disease Models, Animal ; Immunologic Factors ; therapeutic use ; Interferon-alpha ; therapeutic use ; Interleukin-10 ; metabolism ; Kidney ; metabolism ; Male ; Pancreatitis, Acute Necrotizing ; drug therapy ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

BACKGROUNDIt is well known that dehydration can impair bodily functions. To evaluate the impact of hydration status under ambient environmental temperature on the immune system, 25 male collegiate wrestlers were recruited to undergo an experimental dehydration program.

METHODSThirteen subjects had controlled diets with individual energy requirements to prevent body mass loss and restricted water intake to cause 4.52% dehydration; they formed the dehydrated group (DE). These subjects developed a urine specific gravity of about 1.030 in 84 hours. Twelve other subjects had no water restriction and maintained their total body weight comprised the euhydrated group (EU). Peripheral blood monocytes (PBMNC) were isolated after dehydration to perform immune response testing by being incubated with a polysaccharide fraction from fu-ling, Poria cocos (polysaccharide fraction from Poria cocos, PCPS, 1 - 30 £g/L), to prepare a conditioned medium termed conditioned medium of PBMNC stimulated by PCPS (PCPS-MNC-CM). More PCPS (25 µg/L) was needed in the DE group to prepare the PCPS-MNC-CM, which was assayed with a growth inhibitory curve for treated U973 cells.

RESULTSThe treated U937 cells, incubated together with PCPS-MNC-CM from the DE group, exhibited a much lower nitroblue tetrazolium (NBT) positive value of (63.7 ± 4.7)%. The concentration of interferon-gamma (IFN-γ), interleukin (IL)-1β and tumor necrosis factor (TNF)-α in PCPS-MNC-CM from subjects after dehydration was much lower than in the CM from the EU group.

CONCLUSIONThe immune response to PCPS in the DE group was lower than in normally hydrated subjects.

Adolescent ; Adult ; Dehydration ; physiopathology ; Drugs, Chinese Herbal ; chemistry ; Fever ; Humans ; Immunologic Factors ; Interferon-gamma ; metabolism ; Interleukin-1beta ; metabolism ; Leukocytes, Mononuclear ; drug effects ; metabolism ; Male ; Polysaccharides ; chemistry ; immunology ; Tumor Necrosis Factor-alpha ; metabolism ; U937 Cells ; Universities ; Wolfiporia ; Wrestling ; Young Adult

OBJECTIVETo detect the expression level of interleukin 17 (IL-17) in the plasma and colonic mucosa of patients with ulcerative colitis (UC), and to explore the synergistic mechanism of qingchang huashi recipe (QHR) combined with Mesalazine.

METHODSRecruited were 24 mild or moderate UC patients of damp-heat inner accumulation syndrome (DHIAS). Their samples of intestinal tissues were histologically graded. They were assigned to the combination group and the Western medicine (WM) group, 12 in each group. Besides, another 12 healthy volunteers were recruited as the healthy control group. QHR combined Mesalazine were given to patients in the combination group, while those in the WM group took Mesalazine. The therapeutic course for all was 3 months. By the end of treatment the expression level of IL-17 in the plasma and colonic mucosa was detected using ELISA. The infiltration of IL-17 in the intestinal mucosal tissue was detected by immunohistochemical SP method.

RESULTSThe expression level of IL-17 in the plasma and colonic mucosa was significantly higher in UC patients than in healthy controls (P <0. 05). The higher the histological grading the higher the expression level. The expression level of IL-17 in plasma and colonic tissues decreased after treatment in the two treatment groups (P < 0.05). Besides, the expression level of IL-17 was lower in the combination group than in the WM group (P <0.05).

CONCLUSIONQHR combined Mesalazine could synergically enhance the effect and effectively inhibit intestinal inflammation through down-regulating the expression of IL-17.

Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Colitis, Ulcerative ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Immunologic Factors ; metabolism ; Inflammation ; metabolism ; Interleukin-17 ; metabolism ; Intestinal Mucosa ; drug effects ; Intestines ; metabolism ; Mesalamine ; therapeutic use

OBJECTIVETo evaluate the hepatoprotective and immunotherapeutic effects of aqueous extract of turmeric rhizome in CCl4 intoxicated Swiss albino mice.

METHODSFirst group of mice (n=5) received CCl4 treatment at a dose of 0.5 mL/kg bw (i.p.) for 7 days. Second group was fed orally the aqueous extract of turmeric at a dose of 50 mg/kg bw for 15 days. The third group was given both the turmeric extract (for 15 days, orally) and CCl4 (for last 7 days, i.p.). The fourth group was kept as a control. To study the liver function, the transaminase enzymes (SGOT and SGPT) and bilirubin level were measured in the serum of respective groups. For assaying the immunotherapeutic action of Curcuma longa (C. longa), non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages were studied from the respective groups.

RESULTSThe result of present study suggested that CCl4 administration increased the level of SGOT and SGPT and bilirubin level in serum. However, the aqueous extract of turmeric reduced the level of SGOT, SGPT and bilirubin in CCl4 intoxicated mice. Apart from damaging the liver system, CCl4 also reduced non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages. Administration of aqueous extract of C. longa offered significant protection from these damaging actions of CCl4 on the non specific host response in the peritoneal macrophages of CCl4 intoxicated mice.

CONCLUSIONSIn conclusion, the present study suggests that C. longa has immunotherapeutic properties along with its ability to ameliorate hepatotoxicity.

Animals ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Carbon Tetrachloride ; toxicity ; Cell Adhesion ; drug effects ; immunology ; Curcuma ; chemistry ; Cytotoxicity, Immunologic ; drug effects ; Immunologic Factors ; pharmacology ; Liver ; drug effects ; metabolism ; pathology ; Macrophages, Peritoneal ; drug effects ; immunology ; metabolism ; pathology ; Male ; Mice ; Nitric Oxide ; metabolism ; Peroxidase ; metabolism ; Plant Extracts ; pharmacology ; Protective Agents ; pharmacology

This study examined the subsets of T lymphocytes in the thymus, spleen and mesenteric lymph nodes as well as the subsets of B lymphocytes in the spleen and mesenteric lymph nodes in mice administered chitosan adipate (20 mg/kg) intraperitoneally once or four times at 24 h intervals. The results showed that chitosan adipate decreased the percentage of immature CD4+CD8+ thymic T cells and increased the percentage of mature CD4+ and CD8+ thymocytes. The most significant stimulating effect was observed after four injections. A single exposure to chitosan adipate increased the percentage of CD4+ mesenteric lymph node cells, but four injections of the drug increased the percentage of CD4+ and CD8+ mesenteric lymph node cells. Chitosan adipate had no effect on the subset of splenic T cells. In contrast, chitosan adipate administered either once or four times increased the percentage of CD19+ splenocytes but had no effect on the percentage of CD19+ mesenteric lymph node cells. Overall, chitosan adipate induces the maturation and differentiation of thymocytes, and regulates the number of B splenic cells and lymph node T cells irrespective of the number of doses.
Animals ; B-Lymphocyte Subsets/*drug effects/metabolism ; Chitosan/*analogs&derivatives/*pharmacology ; Dose-Response Relationship, Drug ; Female ; Immunologic Factors/pharmacology ; Lymphoid Tissue/drug effects/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; T-Lymphocyte Subsets/*drug effects/metabolism

OBJECTIVETo explore progesterone-induced blocking factor (PIBF) expression in the placenta and blood of patients with severe preeclampsia and its relationship with immune tolerance imbalance.

METHODSForty-seven patients admitted between January and December, 2012 were enrolled in this study, including 25 patients with early-onset severe preeclampsia (EOPE) and 22 with late-onset severe preeclampsia (LOPE), with 25 women with normal pregnancy serving as control group. The antenatal blood and postpartum placenta were collected for immunohistochemical staining to detect PIBF expression in the placenta and for testing serum PIBF level using ELISA. Flow cytometry was used to detect the percentage of circulating Th1 and Th2 cells and the Th1/Th2 ratio was calculated.

RESULTSPIBF was expressed in decidual cells, syncytiotrophoblasts and partial cytotrophablasts. The serum PIBF levels were 213.58 ± 44.93 ng/ml in EOPE group, 243.00∓61.19 ng/ml in LOPE group and 273.91 ± 48.57 ng/ml in control group. There were significant differences in serum PIBF, blood Th1/Th2 and placenta PIBF-IOD among the 3 groups (P<0.05). EOPE group had significantly lower serum PIBF, lower llacental PIBF quantity (PIBF-IOD) and higher blood Th1/Th2 than the control group (P<0.05). Serum PIBF in women with severe preeclampsia was positively correlated with placenta PIBF-IOD and negatively with blood Th1/Th2 ratio (P<0.05), but a negative correlation between serum PIBF and 24-hour urinary protein was found only in EOPE group (P<0.05).

CONCLUSIONThe immune tolerance imbalance mediated by PIBF may participate in the pathogenesis of severe preeclampsia. PIBF, the immune suppressor secreted by lymphocytes of pregnancy women, is also a protective factor against severe preeclampsia, which is expected to be a new target in therapy.

Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immune Tolerance ; Placenta ; metabolism ; Pre-Eclampsia ; immunology ; Pregnancy ; Pregnancy Proteins ; blood ; metabolism ; Suppressor Factors, Immunologic ; blood ; metabolism ; Th1-Th2 Balance