To establish optimal reference values for recovered immune cell subsets, we prospectively investigated post-transplant immune reconstitution (IR) in 144 patients who received allogeneic stem cell transplantation (allo- SCT) and without showing any of the following events: poor graft function, grades II‒IV acute graft-versus-host disease (GVHD), serious chronic GVHD, serious bacterial infection, invasive fungal infection, or relapse or death in the first year after transplantation. IR was rapid in monocytes, intermediate in lymphocytes, CD3 Tcells, CD8 T cells, and CD19 B cells, and very slow in CD4 T cells in the entire patient cohort. Immune recovery was generally faster under HLA-matched sibling donor transplantation than under haploidentical transplantation. Results suggest that patients with an IR comparable to the reference values display superior survival, and the levels of recovery in immune cells need not reach those in healthy donor in the first year after transplantation.We suggest that data from this recipient cohort should be used as reference values for post-transplant immune cell counts in patients receiving HSCT.
Adolescent ; Adult ; Child ; Child, Preschool ; China ; Disease-Free Survival ; Female ; Graft vs Host Disease ; immunology ; mortality ; HLA Antigens ; immunology ; Hematopoietic Stem Cell Transplantation ; Humans ; Immune Reconstitution ; Male ; Middle Aged ; Reference Values ; Siblings ; T-Lymphocytes ; immunology ; Tissue Donors ; Transplantation, Homologous ; Young Adult

Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths worldwide. Although progress in the treatment of advanced non-small cell lung cancer (NSCLC) has been made over the past decade, the 5-year survival rate in patients with lung cancer remains only 10%–20%. Obviously, new therapeutic options are required for patients with advanced NSCLC and unmet medical needs. Cancer immunotherapy is an evolving treatment modality that uses a patient's own immune systems to fight cancer. Theoretically, cancer immunotherapy can result in long-term cancer remission and may not cause the same side effects as chemotherapy and radiation. Immuno-oncology has become an important focus of basic research as well as clinical trials for the treatment of NSCLC. Immune checkpoint inhibitors are the most promising approach for cancer immunotherapy and they have become the standard of care for patients with advanced NSCLC. This review summarizes basic tumor immunology and the relevant clinical data on immunotherapeutic approaches, especially immune checkpoint inhibitors in NSCLC.
Allergy and Immunology ; Carcinoma, Non-Small-Cell Lung ; Cell Cycle Checkpoints ; Drug Therapy ; Humans ; Immune System ; Immunotherapy ; Lung Neoplasms ; Standard of Care ; Survival Rate

OBJECTIVEThe current study aims to investigate the effect of Hemagglutinating virus of Japan envelope (HVJ-E) on induction of apoptosis and autophagy in human prostate cancer PC3 cells, and the underlying mechanisms.

METHODSPC3 cells were treated with HVJ-E at various multiplicity of infection (MOI), and the generated reactive oxygen species (ROS), cell viability, apoptosis, and autophagy were detected, respectively. Next, the role of ROS played in the regulation of HVJ-E-induced apoptosis and autuphagy in PC3 cells were analysed. In the end, the relationship between HVJ-E-induced apoptosis and autuophagy was investigated by using rapamycin and chloroquine.

RESULTSFlow cytometry assay revealed that HVJ-E treatment induced dose-dependent apoptosis and that the JNK and p38 MAPK signaling pathways were involved in HVJ-E-induced apoptosis in PC3 cells. In addition, HVJ-E was able to induce autophagy in PC3 cells via the class III PI3K/beclin-1 pathway. The data also implyed that HVJ-E-triggered autophagy and apoptosis were ROS dependent. When ROS was blocked with N-acetylcysteine (NAC), HVJ-E-induced LC3-II conversion and apoptosis were reversed. Interestingly, HVJ-E-induced apoptosis was significantly increased by an inducer of autophagy, rapamycin pretreatment, both in vitro and in vivo.

CONCLUSIONHVJ-E exerts anticancer effects via autophagic cell death in prostate cancer cells.

Apoptosis ; physiology ; Autophagy ; physiology ; Cell Line, Tumor ; Cell Survival ; Humans ; Male ; Oncolytic Virotherapy ; Prostatic Neoplasms ; metabolism ; Reactive Oxygen Species ; metabolism ; Sendai virus ; immunology ; physiology ; Virus Inactivation

OBJECTIVETo investigate the risk stratification of aggressive B cell lymphoma using the immune microenvironment and clinical factors.

METHODSA total of 127 patients with aggressive B cell lymphoma between 2014 and 2015 were enrolled in this study. CD4, Foxp3, CD8, CD68, CD163, PD-1, and PD-L1 expression levels were evaluated in paraffin-embedded lymphoma tissues to identify their roles in the risk stratification. Eleven factors were identified for further evaluation using analysis of variance, chi-square, and multinomial logistic regression analysis.

RESULTSSignificant differences in 11 factors (age, Ann Arbor stage, B symptom, ECOG performance status, infiltrating CD8+ T cells, PD-L1 expression, absolute blood monocyte count, serum lactate dehydrogenase, serum iron, serum albumin, and serum β2-microglobulin) were observed among patient groups stratified by at least two risk stratification methods [International Prognostic Index (IPI), revised IPI, and NCCN-IPI models] (P < 0.05). Concordance rates were high (81.4%-100.0%) when these factors were used for the risk stratification. No difference in the risk stratification results was observed with or without the Ann Arbor stage data.

CONCLUSIONWe developed a convenient and inexpensive tool for use in risk stratification of aggressive B cell lymphomas, although further studies on the role of immune microenvironmental factors are needed.

Adult ; Biomarkers, Tumor ; Gene Expression Regulation, Neoplastic ; immunology ; Humans ; Lymphoma, B-Cell ; classification ; pathology ; Prognosis ; Retrospective Studies ; Survival Analysis

No abstract available.
Adult ; Female ; Graft Rejection/immunology/*prevention & control ; Graft Survival ; *Hematopoietic Stem Cell Transplantation ; Humans ; *Immune Tolerance ; Immunosuppressive Agents/therapeutic use ; Kidney Failure, Chronic/diagnosis/*surgery ; *Kidney Transplantation ; Living Donors ; Siblings ; Time Factors ; *Transplantation Chimera ; Treatment Outcome

BACKGROUND/AIMS: The purpose of this study was to determine the correlations between inflammatory factors-including absolute lymphocyte count, lactate dehydrogenase, beta2-microglobulin, albumin, C-reactive protein, and ferritin-and the prognosis for survival in patients with multiple myeloma (MM) treated with induction chemotherapy containing thalidomide and who underwent autologous stem cell transplantation (ASCT). METHODS: Data from patients at 13 university hospitals in South Korea were collected retrospectively between December 2005 and May 2013. RESULTS: The median age of the 232 patients was 57 years (range, 33 to 77) and the male to female ratio was 1.09:1. In the multivariate analysis, fewer than two combined abnormal inflammatory factors was the only independent prognostic factor for superior progression-free survival (relative risk [RR], 0.618; 95% confidence interval [CI], 0.409 to 0.933; p = 0.022), and platelet count > 100 x 109/L and fewer than two combined abnormal inflammatory factors were independent prognostic factors for superior overall survival (RR, 4.739; 95% CI, 1.897 to 11.839; p = 0.001 and RR, 0.263; 95% CI, 0.113 to 0.612; p = 0.002, respectively). CONCLUSIONS: Patients with two or more than two combined inflammatory factors who were treated with thalidomide induction chemotherapy and who underwent ASCT showed significantly shorter survival compared to those with fewer than two combined inflammatory factors. These results could be helpful for predicting prognosis in patients with MM.
Adult ; Aged ; Antineoplastic Agents/adverse effects/*therapeutic use ; Biomarkers, Tumor/*blood ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Hospitals, University ; Humans ; Induction Chemotherapy ; Inflammation Mediators/*blood ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multiple Myeloma/blood/diagnosis/*drug therapy/immunology/mortality ; Multivariate Analysis ; Neoadjuvant Therapy ; Odds Ratio ; Proportional Hazards Models ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Stem Cell Transplantation ; Thalidomide/adverse effects/*therapeutic use ; Time Factors ; Transplantation, Autologous ; Treatment Outcome

The aim of this study was to investigate the anti-inflammatory effect of Guizhi Fuling capsule and its active complex (consistent of 15 active compounds) on LPS-induced RAW264. 7 cells. The effect of Guizhi Fuling capsule and its active complex on cell viability in RAW264. 7 cells were determined by MTT assay. The inhibitory effect of Guizhi Fuling capsule and active complex on the releasing of IL-1β, TNF-α and PGE2 induced by LPS in RAW264. 7 cells was detected by ELISA assay. The expression of IL-1β and mPGES-1 in Guizhi Fuling capsule or active complex treated RAW264. 7 cells was examined by Western blot assay. Guizhi Fuling capsule and active complex showed no significant effect on the cell viability in RAW264. 7 cells at doses range from 12.5 to 400 mg x L(-1). Compared with LPS treated group, Guizhi Fuling capsule and active complex dose dependently reduced the releasing of IL-1β, TNF-α and PGE2 induced by LPS in RAW264. 7 cells. Moreover, the expression of IL-1β and mPGES-1 was decreased after Guizhi Fuling capsule and active complex treatment, which might contribute to the inhibitory effect of Guizhi Fuling capsule in the releasing of IL-1β, TNF-α and PGE2. This study provided the evidence that Guizhi Fuling capsule and active complex remarkably inhibited the releasing of IL-1β, TNF-α and PGE2induced by LPS in RAW264. 7 cells by reducing the expression IL-1β and mPGES-1. This study provided an experimental basis of Guizhi Fuling capsule for the treatment of inflammation and a theoretical basis for the development of effective compounds of Guizhi Fuling capsule.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Cell Line ; Cell Survival ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Inflammation ; immunology ; Interleukin-1beta ; immunology ; Macrophages ; drug effects ; immunology ; Mice ; Tumor Necrosis Factor-alpha ; immunology

OBJECTIVE: To perform a Meta-analysis of all randomized controlled trials that compared the efficacy and adverse events profile of Mabs for LA HNSCC. METHOD: Several databases were searched, including CBM, PUBMED, EMBASE, and CENTRAL. Primary outcomes included overall response rate (ORR), overall survival (OS), progression-free survival (PFS). Secondary outcomes included serious adverse events, such as grade 3-4 skin reaction, dysphagia, mucositis, and nausea/vomiting. The results were expressed as relative ratio (RR) or hazard rate (HR) with their corresponding 95% CI. RESULT: The final analysis included 10 trials. The primary analyses indicated that Mabs did not improve ORR and PFS, except OS for locoregionally advanced (LA) HNSCC [ORR 1.21, 95% CI (0.97 - 1.49); PFS 0.87, 95% CI (0.75 - 1.01); OS 0.82, 95% CI (0.71 - 0.95)]. Analysis of adverse effects demonstrated that grade 3 - 4 skin reaction ERR 1.87, 95% CI (1.11 - 3.16)] was statistically significantly associated with Mabs except dysphagia ERR 0. 95, 95% CI (0.75 - 1.19)], Mucositis ERR 1.03, 95% CI (0.67 - 1.57)], and nausea/vomiting ERR 1.15, 95% CI (0.71 - 1.86)]. CONCLUSION Anti-EGFR Mabs may be satisfactory for improving OS of LA HNSCC. During the Mabs therapy, skin reaction should be much more monitored.
Antibodies, Monoclonal ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; Disease-Free Survival ; ErbB Receptors ; immunology ; Head and Neck Neoplasms ; drug therapy ; Humans ; Randomized Controlled Trials as Topic ; Squamous Cell Carcinoma of Head and Neck

This study discusses the effects of Shenlian extracts (SL) on M1 macrophages in atherosclerosis. The MTT assay was used to detect the growth inhibition rates of RAW264.7 cells. RAW264.7 cells were stimulated with murine interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS) to induce M1 macrophages. The different concentrations of SL extracts (high-dose 50 mg x L(-1), moderate-dose 25 mg x L(-1), low-dose 12.5 mg x L(-1)) were added. The CD86 of M1 macrophages in cell membrane was measured by flow cytometry. The mRNA expression of iNOS and TNF-alpha gene was detected by reverse transcription PCR (RT-PCR). And the supernatants were collected, the content of IL-6 and TNF-alpha were detected with ELISA kits. The results of this experiment show that the expression of the cell membrane molecule CD86, iNOS and TNF-alpha gene, the content of IL-6 and TNF-alpha was obviously increased in M1 macrophages by IFN-gamma and LPS. The different doses of SL extract could reduce the expression of the above indicators. The above experimental results demonstrate that IFN-gamma combined LPS can induce RAW264.7 cell to type into M1 macrophages, and SL extracts can inhibit M1 macrophages.
Animals ; Cell Line ; Cell Shape ; drug effects ; Cell Survival ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Interferon-gamma ; genetics ; immunology ; Interleukin-6 ; genetics ; immunology ; Macrophages ; cytology ; drug effects ; immunology ; Mice ; Tumor Necrosis Factor-alpha ; genetics ; immunology

This study was aimed to elucidate the expression of costimulatory molecule CD80 and CD86 in HL-60 cells induced by proteasome inhibitor MG132 and its effect on allogeneic mixed lymphocyte reaction. Acute myelocytic leukemia cell line HL-60 and chronic myelocytic leukemia cell line K562 were cultured. The viability of the cells was measured by flow cytometry. Proteasome inhibitor MG132 at the concentrations of 2 or 3 µmol/L was used to stimulate the HL-60 cell cultured for 24 h and 48 h respectively, and the Annexin V/7-AAD staining and flow cytomotry were used to detect the apoptosis of the HL-60 cells. HL-60 and K562 cells were treated with 1 µmol/L MG132 for 24 h and 48 h respectively, then CD80 and CD86 antibodies were added, finally the expression of CD80 and CD86 was analysed by flow cytomery. The mRNA expression of CD86 in the HL-60 cells treated with 1 µmol/L MG132 was detected by RT-PCR. HL-60 and K562 cells were treated by 1 µmol/L MG132 and then underwent irradiation of 75 Gy (60)Co to kill the cells with their antigenicity preserved. Peripheral blood mononuclear cells (PBMNCs) of healthy volunteers, as reactive cells, were isolated and inoculated into the (60)Co irradiated HL-60 cells of different concentrations, as stimulating cells, CCK-8 was added and then the A value of absorbance was measured at the wave length of 450 nm in an enzyme labeling instrument. The results showed that the cell viability of the HL-60 cells treated with 1 µmol/L MG132 for 24 h an d 48 h was 92.95% and 85.87% respectively. The apoptotic rates of the HL-60 cells treated with MG132 increased in dose-and time-dependent manner. High-concentration of MG132 directly killed HL-60 cells. Before MG132 treatment K562 cells did not express CD86, but the CD86 expression of the HL-60 cells was up-regulated time-dependently after MG132 treatment (P < 0.01). The mRNA expression of CD86 in the HL-60 treated with MG132 was up-regulated time-dependently (P < 0.01). CCK-8 test showed that the proliferation level of PBMNC gradually increased along with the concentration of HL-60 cells treated with MG132 and reached its peak when the concentration of the HL-60 cells was 1×10(5) (P < 0.01). No remarkable proliferation of PBMNC was observed in the K562 groups no matter if the HL-60 cells had been treated with MG132. It is concluded that the high concentration of MG132 can directly kill HL-60 cells, low-concentration of MG132 can induce the expression of costimulatory molecule CD86 in HL-60 cells, also can improve the proliferation of PBMNC.
Apoptosis ; B7-2 Antigen ; immunology ; Cell Survival ; Flow Cytometry ; HL-60 Cells ; Humans ; K562 Cells ; Leukocytes, Mononuclear ; drug effects ; Leupeptins ; pharmacology ; Lymphocyte Culture Test, Mixed ; Proteasome Inhibitors ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Up-Regulation