Cytokines are secreted by various cell types and act as critical mediators in many physiological processes, including immune response and tumor progression. Cytokines production is precisely and timely regulated by multiple mechanisms at different levels, ranging from transcriptional to post-transcriptional and posttranslational processes. Monocyte chemoattractant protein-1 induced protein 1 (MCPIP1), a potent immunosuppressive protein, was first described as a transcription factor in monocytes treated with monocyte chemoattractant protein-1 (MCP-1) and subsequently found to possess intrinsic RNase and deubiquitinase activities. MCPIP1 tightly regulates cytokines expression via various functions. Furthermore, cytokines such as interleukin 1 beta (IL-1B) and MCP-1 and inflammatory cytokines inducer lipopolysaccharide (LPS) strongly induce MCPIP1 expression. Mutually regulated MCPIP1 and cytokines form a complicated network in the tumor environment. In this review, we summarize how MCPIP1 and cytokines reciprocally interact and elucidate the effect of the network formed by these components in cancer-related immunity with aim of exploring potential clinical benefits of their mutual regulation.
Chemokine CCL2/immunology* ; Humans ; Interleukin-1beta/immunology* ; Neoplasm Proteins/immunology* ; Neoplasms/pathology* ; Ribonucleases/immunology* ; Transcription Factors/immunology*

OBJECTIVETo prepare tumor antigen peptides from HL-60 cells and to induce specific immune response.

METHODSHL-60 antigen peptides were obtained using techniques including freezing and thawing, heat precipitation and acid precipitation. The stimulating effect of the in vitro Hsp70 binding HL-60 peptides on PBMC and the proliferation of stimulated PBMC were observed by T cell activation test. The cytotoxicity of proliferated PBMC is detected by incubating HL-60 cells or K562 cells with PBMC respectively.

RESULTSThe obtained tumor antigen peptides were a peptides mixture. The mixed peptides could activate PBMC and cause PBMC proliferation in vitro after presented by Hsp70. The proliferated PBMC showed specific cytotoxicity to HL-60 cells but not to K562 cells.

CONCLUSIONThe method for preparing of human leukemia tumor antigen peptides used in this paper is simple and easy; the obtained antigen peptides can induce specific immune response in vitro.

Cell Division ; HL-60 Cells ; HSP70 Heat-Shock Proteins ; immunology ; Humans ; K562 Cells ; Killer Cells, Natural ; immunology ; Leukocytes, Mononuclear ; cytology ; immunology ; Neoplasm Proteins ; immunology ; Peptides ; immunology

OBJECTIVETo develop a therapeutic vaccine against human tumors associated with human papillomavirus type 16E6E7 (HPV16E6E7) which is modified from a Chinese patient of the cervical cancer which possessing the antigenicity and no transforming activity, and explore more active vaccine for inducing cellular immunity with mouse co-stimulatory molecular B7-1 gene.

METHODSThe modified E6E7 gene expression plasmid pVR1012-fmE6E7 was constructed and transfected Cos-7 cells, and the E7 protein specific expression was testified by immunofluorescence assay. C57BL/6 mice were immunized intramuscularly with pVR1012-fmE6E7 alone or in combination with B7-1 gene expression plasmid (pcDNA3.1-B7-1). The activity of cytotoxic T lymphocytes (CTLs) was analyzed with 51Cr specific release assay and the specific antibody in sera was analyzed by indirect ELISA. HPV16 positive C57BL/6 tumor cells C3 were inoculated subcutaneously in the vaccinated mice to assay the growth of transplanted tumors.

RESULTSThe specific CTLs and antibody from immunized mice were induced efficaciously by the E6E7 gene immunization, and co-administration of B7-1 gene could significantly enhanced the CTLs immune responses of fmE6E7, and protected 33% immunized mice against C3 tumor cells challenge. In contrast, all the mice immunized only with fmE6E7 gene developed transplanted tumors after C3 cells challenge. There was no difference in E7 specific antibody responses between mice immunized with the E6E7 gene only and co-administration with B7-1 gene.

CONCLUSIONSThe modified E6E7 gene can be used as target gene for developing DNA vaccine, and B7-1 gene may represent an attractive adjuvant for enhancement of the specific cellular immune responses.

Animals ; Antibodies, Neoplasm ; immunology ; B7-1 Antigen ; genetics ; immunology ; Female ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Oncogene Proteins, Viral ; genetics ; immunology ; Papillomavirus E7 Proteins ; Repressor Proteins ; T-Lymphocytes, Cytotoxic ; immunology ; Transfection ; Uterine Cervical Neoplasms ; immunology ; pathology ; virology ; Vaccines, DNA ; immunology

Animals ; B7-H1 Antigen ; immunology ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; immunology ; Humans ; Interferons ; immunology ; Mice ; Neoplasm Proteins ; immunology ; Neoplasms ; immunology ; Up-Regulation ; immunology

Antineoplastic Agents, Immunological ; immunology ; pharmacology ; Cell Line, Tumor ; GPI-Linked Proteins ; antagonists & inhibitors ; immunology ; Humans ; Neoplasm Proteins ; analysis ; immunology ; Pancreatic Neoplasms ; drug therapy ; immunology ; pathology

A mouse-anti-human monoclonal antibody was produced by using the membrane proteins of human lung carcinoma cell line A549 as the immunogen to generate monoclonal antibodies against lung carcinoma with the use of hybridoma techniques. McAb4E7 was prepared successfully. To identify its antigen, proteomic technologies such as two-dimenstional electrophoresis, western blotting and mass spectrometry were employed. The targeting antigen of McAb4E7 expressed positive in human lung cancer cell lines A549 and human hepatocarcinoma cell line HepG2, moreover, the expression of the antigen was stronger in A549 cells. Finally, we obtained one positive protein in A549 cell line that has strong affinity and specificity for McAb4E7, which was identified to be ATP synthase beta subunit. We identified ATP synthase beta subunit as the targeting antigen of lung carcinoma special monoclonal antibody McAb4E7.
Animals ; Antibodies, Monoclonal ; biosynthesis ; chemistry ; immunology ; Antibodies, Neoplasm ; immunology ; Antibody Specificity ; Antigens, Neoplasm ; genetics ; immunology ; Cell Line, Tumor ; Humans ; Lung Neoplasms ; immunology ; Membrane Proteins ; immunology ; Mice ; Mice, Inbred BALB C ; Mitochondrial Proton-Translocating ATPases ; immunology

Prostate stem cell antigen (PSCA) is a cell surface antigen expressed in normal prostate and overexpressed in cancers associated with prostate, bladder and pancreas. The sensitivity of PSCA labeling is higher than PSA in prostate cancer. PSCA can be used in the preparation of protein vaccine and nucleic acid vaccine. Further studies are required to confirm its safety and efficacy as a diagnostic means.
Antigens, Neoplasm ; GPI-Linked Proteins ; Humans ; Immunotherapy ; Male ; Membrane Glycoproteins ; analysis ; genetics ; immunology ; Neoplasm Proteins ; analysis ; genetics ; immunology ; Pancreatic Neoplasms ; diagnosis ; Prostatic Neoplasms ; diagnosis ; Urinary Bladder Neoplasms ; diagnosis

This study was aimed to establish the reliable genotyping method of human platelet antigens of HPA-15 system by PCR-SSP and to use this assay in the further HPA genotyping of volunteer platelet donors. 3 sequence-specific primers recommended by the 11th Platelet Genotyping and Serology Workshop on behalf of International Society of Blood Transfusion (ISBT) were synthesized. The concentration of each primer pair, the concentration of Mg(2+) and the PCR conditions were adjusted to optimize the conditions so that HPA-15 system could be specific amplified. The accuracy and reliability of the developed assay was evaluated and confirmed by typing the coded DNA samples provided by the 11th Platelet Genotyping and Serology Workshop. As a parallel control, a total of 50 volunteer platelet donors in Shenzhen were genotyped by both our assay and the G&T commercial kit at HPA-15 system. 10 coded samples distributed by the 11th Platelet Genotyping and Serology Workshop were genotyped by established PCR-SSP method. The results showed that a concordance rate of 100% was observed between the results obtained by established PCR-SSP method and the results provided by ISBT report. The HPA gene frequencies observed in 50 randomly-selected platelet donors in Shenzhen were 0.5100 and 0.4900 for HPA-15a and HPA-15b respectively. In conclusion, PCR-SSP assay established in our study provides a simple, rapid and accurate method for HPA-15 system genotyping, which assay is suitable for routine clinical HPA genotyping and shows a broad prospect in its further applications.
Antigens, CD ; genetics ; immunology ; Antigens, Human Platelet ; genetics ; GPI-Linked Proteins ; Genotype ; Humans ; Isoantigens ; genetics ; immunology ; Neoplasm Proteins ; genetics ; immunology ; Polymerase Chain Reaction ; methods ; Polymorphism, Single-Stranded Conformational

OBJECTIVETo investigate the correlation between BRAF V600E mutation and anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) therapeutic effects in metastatic colorectal cancer.

METHODSStudies were included into meta-analysis to investigate the association between BRAF V600E mutation and clinical outcome in metastatic colorectal cancer patients treated with anti-EGFR MoAbs.

RESULTSA total of 7 studies were included in this meta-analysis. The 7 studies included 1352 patients in total, sample sizes ranged from 67 to 493. Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were collected from included studies and were used to assess the strength of the relation. In patients with wild-type KRAS, the pooled odds ratio for ORR of mutant BRAF over wild-type BRAF was 0.27 (95% CI=0.10-0.70). BRAF mutation predicted a deterioration in PFS and OS in wild-type KRAS patients treated with anti-EGFR MoAbs (hazard ratio=2.78, 95% CI=1.62-4.76; hazard ratio=2.54, 95% CI=1.93-3.32).

CONCLUSIONBRAF V600E mutation is related to lack of response and worse survival in wild-type KRAS metastatic colorectal cancer patients treated with anti-EGFR MoAbs.

Antibodies, Monoclonal ; immunology ; Colorectal Neoplasms ; immunology ; pathology ; Humans ; Mutation ; Neoplasm Metastasis ; immunology ; Proto-Oncogene Proteins B-raf ; genetics ; Receptor, Epidermal Growth Factor ; immunology

OBJECTIVETo identify cancer-derived immunoglobulin G (IgG) whole molecule-interacting proteins to provide important clues for studying IgG biological functions.

METHOSHeLa cell lysate was immunoprecipitated with rabbit antihuman IgG whole molecule antibody and normal rabbit IgG. The immunocomplex underwent sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and was detected with silver staining. Three prominently enhanced bands were subjected to protein identification with liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the MS data were analyzed with Swiss-Prot database. Cancer-derived IgG whole molecule-interacting proteins were screened and functionally annotated.

RESULTS AND CONCLUSIONWe identified 6 potential cancer-derived IgG whole molecule-interacting proteins with co-immunoprecipitation combined with LC-MS/MS, which provides valuable clues for studying the function of cancer-derived IgG.

Antibodies, Neoplasm ; immunology ; Chromatography, Liquid ; Electrophoresis, Polyacrylamide Gel ; HeLa Cells ; Humans ; Immunoglobulin G ; immunology ; Neoplasms ; immunology ; Proteins ; immunology ; Tandem Mass Spectrometry