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Changes in tumor-antigen expression profile as human small-cell lung cancers progress

Cancer Biology & Medicine 2015年第2期12卷 96-105页

作者： Li-Sheng Ge Neil T. Hoa Nils Lambrecht Maria Dacosta-Iyer Yi Ouyang Amir Abolhoda Martin R. Jadus Research Service VA Long Beach Healthcare System Pathology and Laboratory Medicine Service VA Long Beach Healthcare System Pathology and Laboratory Medicine University of California Surgical Health Care Group Veterans Affairs Medical Center Chao Family Comprehensive Cancer Center UC Irvine School of MedicineUniversity of California

Objective： Our group has previously observed that in patients with small-cell lung cancers （SCLCs）, the expression of a tumor antigen, glioma big potassium （gBK） ion channel, is higher at the time of death than when the cancer is first treated by surgical resection. This study aimed to determine whether this dichotomy was common in other potential lung tumor antigens by examining the same patient samples using our more extensive profile analysis of tumor-antigen precursor protein （TAPP）. We then tested the hypothesis that therapeutic intervention may inadvertently cause this increased gBK production. Methods： SCLC samples （eight surgical resections and three autopsy samples） and three control lungs were examined by quantitative real-time polymerase chain reaction for 42 potential TAPPs that represent potential T-cell-mediated immunological targets. Results： Twenty-two TAPP mRNAs displayed the same profile as gBK, i.e., more mRNAs were expressed at autopsy than in their surgical counterparts. B-cyclin and mouse double minute 2, human homolog of PS3-binding protein were elevated in both autopsy and surgical specimens above the normal-lung controls. When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody. Conclusion： Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.

关键词： Small-cell lung cancer (SCLC) glioma big potassium (gBK) ion channel tumor antigens immunoprevention real-timepolymerase chain reaction T-lymphocytes

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Trap1a is an X-linked and cell-intrinsic regulator of thymocyte development

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Cellular & Molecular Immunology 2017年第8期14卷 685-692页

作者： Chi-Shan Li Fei Tang Peng Zhang Taijiao Jiang Thomas L Saunders Pan Zheng Yang Liu Institute of Biomedical Sciences Academia SinicaTaipeiTaiwanChina Center for Cancer and Immunology Research Children’s National Medical CenterWashingtonDCUSA Institute of Biophysics Chinese Academy of ScienceBeijingChina Department of Internal Medicine School of MedicineUniversity of MichiganAnn ArborMIUSA

The X-linked Trap1a gene encodes the tumor rejection antigen P1A,which is expressed in fetal tissues and multiple lineages of tumor *** function of this gene remains *** chimeric mice with wild-type(WT)and Trap1a^(−/y)bone marrow,we show that Trap1a^(−/y)donor cells are capable of generating most lineages of hematopoietic cells,with the notable exception of T *** of Trap1a selectively arrests T-cell development at double-negative stage 1(DN1,with a CD4^(−)CD8^(−)CD25^(−)CD44^(+)phenotype).Because Trap1a is expressed in Lin^(−)Sca-1^(+)c-Kit^(+)and common lymphoid progenitors but not in immature thymocytes(DN1-DN4),Trap1a mutations affect the differentiation potential of progenitor cells without directly acting on T *** a similarity in the blockade of DN1 to DN2 transition,the Trap1a^(−/y)DN1 cells have normal expression of c-Kit,in contrast to what was reported in the Notch1^(−/−)*** DNA profiling of Trap1a^(−/y)and WT embryonic stem cells shows that Trap1a does not regulate the Notch *** data reveal that Trap1a is an X-linked regulator that affects the differentiation potential of progenitor cells into T cells through a Notch-independent mechanism and identify an important function for the Trap1a gene.

关键词： Notch tumor antigens T cell development

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Finding neoepitopes in mouse models of personalized cancer immunotherapy

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Frontiers in Biology 2016年第5期11卷 366-375页

作者： Sahar Al Seesi Alok Das Mohapatra Arpita Pawashe Ion I. Mandoiu Fei Duan Department of Immunology and Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Cancer Center Farmington CT 06030 USA Department of Computer Science & Engineering University of Connecticut Storrs CT 06269 USA

BACKGROUND： Cancer immunotherapy uses one＇s own immune system to fight cancerous cells. As immune system is hard- wired to distinguish self and non-self, cancer immunotherapy is predicted to target cancerous cells specifically, therefore is less toxic than chemotherapy and radiation therapy, two major treatments for cancer. Cancer immunologists have spent decades to search for the specific targets in cancerous cells. METHODS： Due to the recent advances in high throughput sequencing and bioinformatics, evidence has merged that the neoantigens in cancerous cells are probably the cancer-specific targets that lead to the destruction of cancer. We will review the transplantable murine tumor models for cancer immunotherapy and the bioinformatics tools used to navigate mouse genome to identify tumor-rejecting neoantigens. RESULTS： Several groups have independently identified point mutations that can be recognized by T cells of host immune system. It is consistent with the note that the formation ofpeptide-MHC I-TCR complex is critical to activate T cells. Both anchor residue and TCR-facing residue mutations have been reported. While TCR-facing residue mutations may directly activate specific T cells, anchor residue mutations improve the binding of peptides to MHC I molecules, which increases the presentation of peptides and the T cell activation indirectly. CONCLUSIONS： Our work indicates that the affinity of neoepitopes for MHC I is not a predictor for anti-tumor immune responses in mice. Instead differential agretopic index （DAI）, the numerical difference of epitope-MHC I affinities between the mutated and un-mutated sequences is a significant predictor. A similar bioinformatics pipeline has been developed to generate personalized vaccines to treat human ovarian cancer in a Phase I clinical trial.

关键词： cancer immunotherapy tumor antigens neoantigens neoepitopes differential agretopic index (DAI) RNA-Seq single nucleotide variant (SNV)

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SIGNIFICANCE OF EXPRESS OF SOME NONHORMONAL antigens IN PANCREATIC ENDOCRINE tumorS

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Chinese Journal of Cancer Research 1998年第3期10卷 57-60页

作者：虞积耀 General Hospital of the Navy Beijing

Objective: To study the express of some nonhormonal antigens in pancreatic endocrine tumors. Methods: The nonhormonal antigens including Alpha subunit of human chorionic gonadotropin (α HCG), progesterone receptors (PR), 7B2, HISL 19, in normal pancreatic islets and in 52 cases of pancreatic endocrine tumors (PET) were investigated by immunohistochemistry. Results: It was found that HCG can be detected in PET but not in normal islet cells. HCG immunoreactivity was expressed by 3 of 28 (10.7%) benign PET and by 14 of 24 (58.3%) malignant *** was found by 20 of 28(71.4%) benign PET and by 7 of 24 (29%) malignant PET. 7B2 was detected by 23 of 28 (82.1%) benign PET and by 13 of 24 (54.2%) malignant PET. HISL 19 was appeared by 23 of 28 benign PET and by 11 of 24 (46%) malignant PET. Golgitype persisted in 87.5% malignant tumors. Conclusion: The assay of nonhormonal antigens may be well defined the clinico pathological characteristics of PET.

关键词： Pancreatic endocrine tumor tumor antigens Immunohistochemistry.

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UNLEASH ANTIGEN-SPECIFIC ANTI-tumor IMMUNITY

UNLEASH ANTIGEN-SPECIFIC ANTI-TUMOR IMMUNITY

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第11次中国实验血液学会议

作者： Department of Pharmacology,Temple University School of Medicine,Philadelphia,PA 19140,U.S.A.Xiao-Feng Yang

＜正＞Significant progresses have led to the renais- sance of tumor immunology and studies on anti- tumor ***,despite of the pro- gress in the field of tumor immunology and immuno- therapy,current antigen-specific immunotherapies for tumors are far less satisfied than expected,which reflects the need to continuously improve our under- standing on tumor immunology and immunobiology per *** this brief review,we outline the progress made in our laboratory as well as in the field with a focus on anti-tumor immunity characterized in he- matologic malignancies in the following topics:（1） successful stories in anti-cancer immunotherapy;（2）tumor antigens in hematologic malignancies;（3）antigenological concepts and principles;（4） stimulation-responsive splicing model in generation of immunogenic tumor antigens;（5）significance of unconventional tumor antigens;（6）improvement of antigen epitope processing;（7）making of more ef- fective dendritic cells;（8）removal of immunosup- pressive regulatory T cells to unleash anti-tumor ira- munity and improve immunotherapy.

关键词： lymphoma leukemia tumor antigens new developments anti-tumor immune responses immunotherapy

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tumor antigen and MHC expression in glioma cells for immunotherapeutic interventions

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World Journal of Immunology 2013年第3期3卷 62-67页

作者： Christina Susanne Mullins Alexander Walter Michael Schmitt Carl-Friedrich Classen Michael Linnebacher Pediatrics Department University Hospital Rostock 18057 Rostock Germany Department of General Surgery Molecular Oncology and Immunotherapy University Hospital Rostock 18057 Rostock Germany Department Internal Medicine V University Hospital Heidelberg 69120 Heidelberg Germany

AIM: To investigate the expression of tumor-antigens and major histocompatibility complex(MHC)-machinery components in glioblastoma multiforme cell lines flow cytometry staining methods were ***: Ten GBM cell lines(three commercially available: U-87 MG, U-138-MG and GMS-10 as well as seven newly established cell lines from individual patients in low-passages: HROG02, HROG04, HROG05, HROG06, HROG10, HROG13 and HROG17) were analyzed for expression of(Ⅰ) general and(Ⅱ) GBMrelated tumor antigens as well as of(Ⅲ) components of the MHC machinery by flow ***: All cell lines expressed MHC class?Ⅰ?with seven out of the ten being HLA-A02 positive. Four of the seven primary cell lines additionally expressedMHC class Ⅱ in a constitutive manner. Of note, after interferon gamma(IFN-γ) treatment, all seven cell lines expressed MHC class Ⅱ. The tumor associated antigens(TAA) EGFR and survivin were expressed at high levels in all cell lines; whereas MART-1, RHAMM, WT-1 and IL-13Rα were expressed by at least half of the cell lines and HER2/neu, MAGE-1 and tyrosinase were expressed only by few cell lines. However, all cell lines expressed at least two of the candidate antigens included into this ***: No obvious differences between commercially available and newly-established cell lines were observed. Thus, the latter in low-passages are interesting for(therapy-) screening and immunotherapeutic strategies.

关键词： tumor antigens Glioblastoma multiforme Major histocompatibility complex molecules tumor models Cell lines

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