Cancer immunity最新文献

NY-ESO-1-specific immunological pressure and escape in a patient with metastatic melanoma. 转移性黑色素瘤患者ny - eso -1特异性免疫压力和逃逸。

Cancer immunity Pub Date : 2013-07-15 Print Date: 2013-01-01

Lotta von Boehmer, Muriel Mattle, Peter Bode, Alexandro Landshammer, Carolin Schäfer, Natko Nuber, Gerd Ritter, Lloyd Old, Holger Moch, Niklaus Schäfer, Elke Jäger, Alexander Knuth, Maries van den Broek

{"title":"NY-ESO-1-specific immunological pressure and escape in a patient with metastatic melanoma.","authors":"Lotta von Boehmer, Muriel Mattle, Peter Bode, Alexandro Landshammer, Carolin Schäfer, Natko Nuber, Gerd Ritter, Lloyd Old, Holger Moch, Niklaus Schäfer, Elke Jäger, Alexander Knuth, Maries van den Broek","doi":"","DOIUrl":"","url":null,"abstract":"During cancer progression, malignant cells may evade immunosurveillance. However, evidence for immunological escape in humans is scarce. We report here the clinical course of a melanoma patient whose initial tumor was positive for the antigens NY-ESO-1, MAGE-C1, and Melan-A. Upon immunization with a recombinant vaccinia/fowlpox NY-ESO-1 construct, the patient experienced a mixed clinical response and spreading of the NY-ESO-1 epitopes in the CD4+ T cell compartment. After NY-ESO-1 protein + CpG immunization, the patient's anti-NY-ESO-1 IgG response increased. Over the following years, progressing lesions were resected and found to be NY-ESO-1-negative while being positive for MAGE-C1, Melan-A, and MHC-I. The fatal, inoperable brain metastasis was analyzed after his death and also proved to be NY-ESO-1-negative, while being positive for MAGE-C1 and Melan-A, as well as MHC-I. We propose that cancer control and cancer escape in this patient were governed by NY-ESO-1-specific immunological pressure. Our findings provide evidence for the existence of immunoediting and immunoescape in this cancer patient. ","PeriodicalId":84394,"journal":{"name":"Cancer immunity","volume":"13 ","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2013-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718732/pdf/130312.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31603699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structured reporting of T cell assay results. T细胞检测结果的结构化报告。

Cancer immunity Pub Date : 2013-07-15 Print Date: 2013-01-01

Sylvia Janetzki, Axel Hoos, Cornelis J M Melief, Kunle Odunsi, Pedro Romero, Cedrik M Britten

引用次数: 0

Human ovarian tumor ascites fluids rapidly and reversibly inhibit T cell receptor-induced NF-κB and NFAT signaling in tumor-associated T cells. 人卵巢肿瘤腹水快速、可逆地抑制T细胞受体诱导的肿瘤相关T细胞中NF-κB和NFAT信号传导。

Cancer immunity Pub Date : 2013-07-15 Print Date: 2013-01-01

Michelle R Simpson-Abelson, Jenni L Loyall, Heather K Lehman, Jennifer L Barnas, Hans Minderman, Kieran L O'Loughlin, Paul K Wallace, Thaddeus C George, Peng Peng, Raymond J Kelleher, Kunle Odunsi, Richard B Bankert

{"title":"Human ovarian tumor ascites fluids rapidly and reversibly inhibit T cell receptor-induced NF-κB and NFAT signaling in tumor-associated T cells.","authors":"Michelle R Simpson-Abelson, Jenni L Loyall, Heather K Lehman, Jennifer L Barnas, Hans Minderman, Kieran L O'Loughlin, Paul K Wallace, Thaddeus C George, Peng Peng, Raymond J Kelleher, Kunle Odunsi, Richard B Bankert","doi":"","DOIUrl":"","url":null,"abstract":"Human memory T cells present in ovarian tumor ascites fluids fail to respond normally to stimulation via the T cell receptor (TCR). This immunosuppression is manifested by decreases in NF-κB and NFAT activation, IFN-γ production, and cell proliferation in response to TCR stimulation with immobilized antibodies to CD3 and CD28. The anergy of the tumor-associated T cells (TATs) is mediated by soluble factors present in ovarian tumor ascites fluids. The non-responsiveness of the T cells is quickly reversed when the cells are assayed in the absence of the ascites fluid, and is rapidly reestablished when a cell-free ascites fluid is added back to the T cells. Based upon the observed normal phosphorylation patterns of the TCR proximal signaling molecules, the inhibition of NF-κB, and NFAT activation in response to TCR stimulation, as well as the ability of the diacylglycerol analog PMA and the ionophore ionomycin to bypass the ascites fluid-induced TCR signaling arrest, the site of the arrest in the activation cascade appears to be at or just upstream of PLC-γ. An identical TCR signaling arrest pattern was observed when T cells derived from normal donor peripheral blood were incubated with either malignant or nonmalignant (cirrhotic) ascites fluids. The immunosuppressive activity of ascites fluids reported here suggests that soluble factors acting directly or indirectly upon T cells present within tumors contribute to the anergy that has previously been observed in T cells derived from malignant and nonmalignant inflammatory microenvironments. The soluble immunosuppressive factors represent potential therapeutic targets for ovarian cancer. ","PeriodicalId":84394,"journal":{"name":"Cancer immunity","volume":"13 ","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2013-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718770/pdf/130314.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31603586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Database of T cell-defined human tumor antigens: the 2013 update. T 细胞定义的人类肿瘤抗原数据库：2013 年更新版。

Cancer immunity Pub Date : 2013-07-15 Print Date: 2013-01-01

Nathalie Vigneron, Vincent Stroobant, Benoît J Van den Eynde, Pierre van der Bruggen

引用次数: 0

An analogue peptide from the Cancer/Testis antigen PASD1 induces CD8+ T cell responses against naturally processed peptide. 来自癌症/睾丸抗原PASD1的类似肽诱导CD8+ T细胞对天然加工肽的反应。

Cancer immunity Pub Date : 2013-07-15 Print Date: 2013-01-01

Nicola Hardwick, Sarah Buchan, Wendy Ingram, Ghazala Khan, Gisella Vittes, Jason Rice, Karen Pulford, Ghulam Mufti, Freda Stevenson, Barbara-ann Guinn

{"title":"An analogue peptide from the Cancer/Testis antigen PASD1 induces CD8+ T cell responses against naturally processed peptide.","authors":"Nicola Hardwick, Sarah Buchan, Wendy Ingram, Ghazala Khan, Gisella Vittes, Jason Rice, Karen Pulford, Ghulam Mufti, Freda Stevenson, Barbara-ann Guinn","doi":"","DOIUrl":"","url":null,"abstract":"We have previously identified the novel Cancer/Testis antigen PASD1 by immunoscreening a testis library with pooled acute myeloid leukemia (AML) patient sera. To develop a cytotoxic T lymphocyte (CTL)-inducing vaccine, we have now investigated the carboxy-terminal region, known to contain serological determinants, for MHC class I (HLA-A⋆0201)-binding peptides. Algorithm-selected natural peptides failed to show detectable HLA-A⋆0201 binding in T2 assays. However, anchor-modified analogue peptides showed enhanced binding, with decreased off-rates. Analogue peptide-loaded antigen-presenting cells (APCs) induced IFN-γ production by T cells from normal donors and patients. In addition, peptide-specific T cells could be expanded from cancer patients by stimulation with the PASD1 analogue peptide Pa14. For clinical application, a DNA fusion gene vaccine encoding Pa14 was designed and tested in \"humanized\" mice. Splenocytes from vaccinated mice showed in vitro cytotoxicity against tumour cells, either exogenously loaded with the corresponding wild-type peptide (Pw8) or expressing endogenously processed PASD1 protein. We show for the first time that a DNA vaccine encoding an altered PASD1 epitope can induce CTLs to target the natural peptide expressed by human tumour cells. ","PeriodicalId":84394,"journal":{"name":"Cancer immunity","volume":"13 ","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2013-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718735/pdf/130316.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31603588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Changes in ovarian tumor cell number, tumor vasculature, and T cell function monitored in vivo using a novel xenograft model. 使用一种新的异种移植模型监测卵巢肿瘤细胞数量、肿瘤血管系统和T细胞功能的变化。

Cancer immunity Pub Date : 2013-05-31 Print Date: 2013-01-01

Sandra J Yokota, John G Facciponte, Raymond J Kelleher, Leonard D Shultz, Jenni L Loyall, Robert R Parsons, Kunle Odunsi, John G Frelinger, Edith M Lord, Scott A Gerber, Sathy V Balu-Iyer, Richard B Bankert

{"title":"Changes in ovarian tumor cell number, tumor vasculature, and T cell function monitored in vivo using a novel xenograft model.","authors":"Sandra J Yokota, John G Facciponte, Raymond J Kelleher, Leonard D Shultz, Jenni L Loyall, Robert R Parsons, Kunle Odunsi, John G Frelinger, Edith M Lord, Scott A Gerber, Sathy V Balu-Iyer, Richard B Bankert","doi":"","DOIUrl":"","url":null,"abstract":"Despite an initial response to chemotherapy, most patients with ovarian cancer eventually progress and succumb to their disease. Understanding why effector T cells that are known to infiltrate the tumor do not eradicate the disease after cytoreduction is critically important to the development of novel therapeutic strategies to augment tumor immunity and improve patient outcomes. Such studies have been hampered by the lack of a suitable in vivo model. We report here a simple and reliable model system in which ovarian tumor cell aggregates implanted intraperitoneally into severely immunodeficient NSG mice establish tumor microenvironments within the omentum. The rapid establishment of tumor xenografts within this small anatomically well-defined site enables the recovery, characterization, and quantification of tumor and tumor-associated T cells. We validate here the ability of the omental tumor xenograft (OTX) model to quantify changes in tumor cell number in response to therapy, to quantify changes in the tumor vasculature, and to demonstrate and study the immunosuppressive effects of the tumor microenvironment. Using the OTX model, we show that the tumor-associated T cells originally present within the tumor tissues are anergic and that fully functional autologous T cells injected into tumor-bearing mice localize within the tumor xenograft. The transferred T cells remain functional for up to 3 days within the tumor microenvironment but become unresponsive to activation after 7 days. The OTX model provides for the first time the opportunity to study in vivo the cellular and molecular events contributing to the arrest in T cell function in human ovarian tumors. ","PeriodicalId":84394,"journal":{"name":"Cancer immunity","volume":"13 ","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2013-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721261/pdf/130211.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31605920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chromosome X-encoded Cancer/Testis antigens are less frequently expressed in non-seminomatous germ cell tumors than in seminomas. 染色体x编码的癌/睾丸抗原在非精原细胞瘤生殖细胞肿瘤中的表达频率低于精原细胞瘤。

Cancer immunity Pub Date : 2013-05-10 Print Date: 2013-01-01

Yao-Tseng Chen, Dengfeng Cao, Rita Chiu, Peishan Lee

{"title":"Chromosome X-encoded Cancer/Testis antigens are less frequently expressed in non-seminomatous germ cell tumors than in seminomas.","authors":"Yao-Tseng Chen, Dengfeng Cao, Rita Chiu, Peishan Lee","doi":"","DOIUrl":"","url":null,"abstract":"Cancer/Testis (CT) antigens are normally only expressed in germ cells and yet are aberrantly activated in a wide variety of human cancers. Most chromosome X-encoded CT antigens (CT-X) show restricted expression in pre-meiotic germ cells in adult testis, except for the expression of SPANX in post-meiotic germ cells. In the present study, the expression of eight CT-X antigens (MAGE-A, NY-ESO-1, GAGE, MAGE-C1/CT7, MAGE-C2/CT10, CT45, SAGE1, and SPANX) in non-seminomatous germ cell tumors was evaluated immunohistochemically, including 24 embryonal carcinomas, 20 yolk sac tumors, 9 teratomas, and 3 choriocarcinomas, and the results were compared to our previous study of 77 classic seminomas and 2 spermatocytic seminomas. SPANX was not detected in any germ cell tumors tested. Spermatocytic seminoma showed strong expression of all CT-X antigens tested (except SPANX), reflecting their origin from adult CT-Xpositive pre-meiotic germ cells. Classic seminomas, originating from prenatal gonocytes, showed widely variable frequency of CT-X antigen expression, ranging from > 80% (CT7, CT10, CT45, and GAGE), 63% (MAGE-A), 18% (NY-ESO-1) to only 4% (SAGE1). In comparison, non-seminomatous germ cell tumors expressed CT-X antigens much less frequently and usually only in small subsets of tumor cells. Intratubular germ cell neoplasia (ITGCN) were mostly CT-X-negative, even in CT-X positive classic seminomas. These findings indicate that CT-X antigens are not expressed in the fetal precursor cells for germ cell tumors, and their expression likely reflects germ cell differentiation of the neoplastic cells (in seminomas) or aberrant gene activation as cancer antigens (in non-seminomatous tumors). ","PeriodicalId":84394,"journal":{"name":"Cancer immunity","volume":"13 ","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2013-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721301/pdf/cim-13-10.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31605919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expression of CD1c enhances human invariant NKT cell activation by α-GalCer. CD1c的表达增强了α-GalCer对人不变NKT细胞的激活作用。

Cancer immunity Pub Date : 2013-05-10 Print Date: 2013-01-01

Lisa M Fox, Jennifer Miksanek, Nathan A May, Louise Scharf, Jennifer L Lockridge, Natacha Veerapen, Gurdyal S Besra, Erin J Adams, Amy W Hudson, Jenny E Gumperz

{"title":"Expression of CD1c enhances human invariant NKT cell activation by α-GalCer.","authors":"Lisa M Fox, Jennifer Miksanek, Nathan A May, Louise Scharf, Jennifer L Lockridge, Natacha Veerapen, Gurdyal S Besra, Erin J Adams, Amy W Hudson, Jenny E Gumperz","doi":"","DOIUrl":"","url":null,"abstract":"Invariant natural killer T (iNKT) cells are innate T lymphocytes that specifically recognize α-linked glycosphingolipids (α-GSLs) as antigens presented by CD1d molecules. Activating iNKT cells by administering α-GSLs improves disease outcomes in murine cancer models and, thus, there is great interest in the clinical potential of these lipids for treating human cancers. However, humans possess several other CD1 isoforms that are not present in mice and it is not clear whether these CD1 molecules, which also bind lipids, affect human iNKT cell responses. We demonstrate here that CD1c, which is co-expressed with CD1d on blood dendritic cells and on a fraction of B cells, is able to present α-galactosylceramide (α-GalCer) as a weak agonist to human iNKT cells, and that the presence of CD1c synergistically enhances α-GalCerdependent activation of iNKT cells by CD1d. Primary human B cells expressing CD1c induced stronger iNKT cell responses to α-GalCer than the CD1c- subset, and an antibody against CD1c inhibited iNKT cell cytokine secretion. These results suggest that therapeutic activation of human iNKT cells by α-GSLs will be driven preferentially by CD1c+ cell types. Thus, B cell neoplasias that co-express CD1c and CD1d may be particularly susceptible to α-GSL therapy, and cancer vaccines using α-GSLs as adjuvants may be most effective when presented by CD1c+ antigen-presenting cells. ","PeriodicalId":84394,"journal":{"name":"Cancer immunity","volume":"13 ","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2013-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721260/pdf/cim-13-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31605918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NKG2D ligands as therapeutic targets. NKG2D配体作为治疗靶点。

Cancer immunity Pub Date : 2013-05-01 Print Date: 2013-01-01

Paul Spear, Ming-Ru Wu, Marie-Louise Sentman, Charles L Sentman

引用次数: 0

Randomized phase I pharmacokinetic study of ipilimumab with or without one of two different chemotherapy regimens in patients with untreated advanced melanoma. ipilimumab在未经治疗的晚期黑色素瘤患者中使用或不使用两种不同化疗方案之一的随机I期药代动力学研究。

Cancer immunity Pub Date : 2013-05-01 Print Date: 2013-01-01

Jeffrey Weber, Omid Hamid, Asim Amin, Steven O'Day, Eric Masson, Stacie M Goldberg, Daphne Williams, Susan M Parker, Scott D Chasalow, Suresh Alaparthy, Jedd D Wolchok

{"title":"Randomized phase I pharmacokinetic study of ipilimumab with or without one of two different chemotherapy regimens in patients with untreated advanced melanoma.","authors":"Jeffrey Weber, Omid Hamid, Asim Amin, Steven O'Day, Eric Masson, Stacie M Goldberg, Daphne Williams, Susan M Parker, Scott D Chasalow, Suresh Alaparthy, Jedd D Wolchok","doi":"","DOIUrl":"","url":null,"abstract":"We describe a randomized three-arm phase I study of ipilimumab administered alone (I group) or in combination with dacarbazine (D group) or carboplatin/paclitaxel (CP group) in patients with previously untreated advanced melanoma. The primary objective was to estimate the effect of ipilimumab on the pharmacokinetics (PK) of dacarbazine and paclitaxel and, conversely, to estimate the effects of dacarbazine and carboplatin/paclitaxel on the PK of ipilimumab. Secondary objectives included evaluation of the safety and anti-tumor activity of ipilimumab when administered alone or with either dacarbazine or carboplatin/paclitaxel, and assessment of pharmacodynamic (PD) effects of ipilimumab on the immune system when administered alone or with either of the two chemotherapies. Ipilimumab was administered at a dose of 10 mg/kg intravenously (IV) every 3 weeks for up to 4 doses. Patients in the D group received dacarbazine 850 mg/m(2) IV every 3 weeks. Patients in the CP group received paclitaxel 175 mg/m(2) IV and carboplatin [AUC=6] IV every 3 weeks. Starting at week 24, patients without dose-limiting toxicities were eligible to receive maintenance ipilimumab at 10 mg/kg every 12 weeks until disease progressed or toxicity required discontinuation. Of 59 randomized patients, 18 (30.5%) discontinued treatment due to adverse events. Response rates by modified WHO criteria were 29.4% (I group), 27.8% (D group), and 11.1% (CP group). No major PK or PD interactions were observed when ipilimumab was administered with dacarbazine or with the carboplatin/paclitaxel combination. This study demonstrated that ipilimumab can be combined safely with two chemotherapy regimens commonly used in advanced melanoma. ","PeriodicalId":84394,"journal":{"name":"Cancer immunity","volume":"13 ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2013-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700777/pdf/cim-13-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31562617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0