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Cancer Immunology Research

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https://www.readbyqxmd.com/read/28314751/identification-of-glycopeptides-as-post-translationally-modified-neoantigens-in-leukemia
#1
Stacy A Malaker, Sarah A Penny, Lora G Steadman, Paisley T Myers, Justin Loke, Manoj Raghavan, Dina L Bai, Jeffery Shabanowitz, Donald Hunt, Mark Cobbold
Leukemias are highly immunogenic but have a low mutational load, providing few mutated peptide targets. Thus, the identification of alternative neoantigens is a pressing need. Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues...
March 17, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28264810/promoter-methylation-modulates-indoleamine-2-3-dioxygenase-1-induction-by-activated-t-cells-in-human-breast-cancers
#2
Satish K Noonepalle, Franklin Gu, Eun-Joon Lee, Jeong-Hyeon Choi, Qimei Han, Jaejik Kim, Maria Ouzounova, Austin Y Shull, Lirong Pei, Pei-Yin Hsu, Ravindra Kohle, Fang Shi, Jiseok Choi, Katie Chiou, Tim H M Huang, Hasan Korkaya, Libin Deng, Hong-Bo Xin, Shuang Huang, Muthusamy Thangaraju, Arun Sreekumar, Stefan Ambs, Shou-Ching Tang, David H Munn, Huidong Shi
Triple-negative breast cancer (TNBC) cells are modulated in reaction to tumor-infiltrating lymphocytes. However, their specific responses to this immune pressure are unknown. In order to address this question, we first used mRNA sequencing to compare the immunophenotype of the TNBC cell line MDA-MB-231 and the luminal breast cancer cell line MCF7 after both were cocultured with activated human T cells. Despite similarities in the cytokine-induced immune signatures of the two cell lines, MDA-MD-231 cells were able to transcribe more IDO1 than MCF7 cells...
March 6, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28254787/serine-proteases-enhance-immunogenic-antigen-presentation-on-lung-cancer-cells
#3
Haley L Peters, Satyendra C Tripathi, Celine Kerros, Hiroyuki Katayama, Haven R Garber, Lisa S St John, Lorenzo Federico, Ismail M Meraz, Jack A Roth, Boris Sepesi, Mourad Majidi, Kathryn Ruisaard, Karen Clise-Dwyer, Jason Roszik, Don L Gibbons, John Heymach, Stephen G Swisher, Chantale Bernantchez, Gheath Alatrash, Samir M Hanash, Jeffrey J Molldrem
Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer in patients; however, the antigenic targets of these re-invigorated T cells remain poorly defined. Lung cancer tumors contain tumor-associated macrophages (TAM) and neutrophils, which release the serine proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor microenvironment. NE and P3 shape the antitumor adaptive immune response in breast cancer and melanoma. In this report, we demonstrate that lung cancer cells cross-presented the tumor-associated antigen PR1, derived from NE and P3...
March 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28254786/clinical-impact-of-tumor-dna-repair-expression-and-t-cell-infiltration-in-breast-cancers
#4
Andrew R Green, Mohammed A Aleskandarany, Reem Ali, Eleanor Grace Hodgson, Suha Atabani, Karen De Souza, Emad Rakha, Ian O Ellis, Srinivasan Madhusudan
Impaired DNA repair drives mutagenicity, which increases neoantigen load and immunogenicity. We investigated the expression of proteins involved in the DNA damage response (ATM, Chk2), double-strand break repair (BRCA1, BLM, WRN, RECQL4, RECQL5, TOPO2A, DNA-PKcs, Ku70/Ku80), nucleotide excision repair (ERCC1), base excision repair (XRCC1, pol β, FEN1, PARP1), and immune responses (CD8, PD-1, PD-L1, FOXP3) in 1269 breast cancers and validated our findings in an independent estrogen receptor (ER)- cohort (n = 279)...
March 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28246107/comprehensive-meta-analysis-of-key-immune-related-adverse-events-from-ctla-4-and-pd-1-pd-l1-inhibitors-in-cancer-patients
#5
Guillermo De Velasco, Youjin Je, Dominick Bossé, Mark M Awad, Patrick A Ott, Raphael B Moreira, Fabio A B Schutz, Joaquim Bellmunt, Guru Sonpavde, F Stephen Hodi, Toni K Choueiri
Immune-related adverse events (irAEs) have been described with immune checkpoint inhibitors (ICIs), but the incidence and relative risk (RR) of irAEs associated with these drugs remains unclear. We selected five key irAEs from treatments with approved cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors (ipilimumab, nivolumab or pembrolizumab, and atezolizumab, respectively) to better characterize their safety profile. We performed a meta-analysis of randomized phase II/III immunotherapy trials, with non-ICI control arms, conducted between 1996 and 2016...
February 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28223282/induction-of-nkg2d-ligands-on-solid-tumors-requires-tumor-specific-cd8-t-cells-and-histone-acetyltransferases
#6
Jiemiao Hu, Chantale Bernatchez, Liangfang Zhang, Xueqing Xia, Eugenie S Kleinerman, Mien-Chie Hung, Patrick Hwu, Shulin Li
NKG2D-mediated immune surveillance is crucial for inhibiting tumor growth and metastases. Malignant tumor cells often downregulate NKG2D ligands to escape from immune surveillance. High-profile studies have shown that restoring NKG2D ligand expression via genetic engineering inhibits tumor formation and progression. However, no effective in vivo approaches are available to restore these ligands across different types of solid tumors because the classic stress signal-dependent induction of this ligand in vitro is transient and has rarely been duplicated in solid tumors in vivo We found that coadministration of an immune stimulatory signal (IL12) and chemotherapy (doxorubicin) restored the NKG2D ligand Rae-1 in multiple tumor types, including a human tumor model...
February 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28159748/estradiol-promotes-breast-cancer-cell-migration-via-recruitment-and-activation-of-neutrophils
#7
Gabriela Vazquez Rodriguez, Annelie Abrahamsson, Lasse Dahl Ejby Jensen, Charlotta Dabrosin
Estradiol (E2) plays a key role in breast cancer progression. Most breast cancer recurrences express the estrogen receptor (ER), but nearly 50% of patients are resistant to antiestrogen therapy. Novel therapeutic targets of ER-positive breast cancers are needed. Protumoral neutrophils expressing the lymphocyte function-associated antigen 1 (LFA-1) integrin may mediate cancer metastasis, and TGFβ1 is the major chemoattractant for neutrophils. The role of E2 in neutrophil-ER(+) breast cancer cell interactions is unknown...
February 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28159747/nk-cell-recruitment-is-necessary-for-eradication-of-peritoneal-carcinomatosis-with-an-il12-expressing-maraba-virus-cellular-vaccine
#8
Almohanad A Alkayyal, Lee-Hwa Tai, Michael A Kennedy, Christiano Tanese de Souza, Jiqing Zhang, Charles Lefebvre, Shalini Sahi, Abhirami A Ananth, Ahmad Bakur Mahmoud, Andrew P Makrigiannis, Greg O Cron, Blair Macdonald, E Celia Marginean, David F Stojdl, John C Bell, Rebecca C Auer
Despite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death from abdominal cancers. Immunotherapies have been effective for selected solid malignancies, but their potential in PC has been little explored. Here, we report that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infected ex vivo with an oncolytic Maraba MG1 virus expressing IL12, promotes the migration of activated natural killer (NK) cells to the peritoneal cavity in response to the secretion of IFNγ-induced protein-10 (IP-10) from dendritic cells...
February 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28148545/tumor-associated-monocytes-macrophages-impair-nk-cell-function-via-tgf%C3%AE-1-in-human-gastric-cancer
#9
Liu-Sheng Peng, Jin-Yu Zhang, Yong-Sheng Teng, Yong-Liang Zhao, Ting-Ting Wang, Fang-Yuan Mao, Yi-Pin Lv, Ping Cheng, Wen-Hua Li, Na Chen, Mubing Duan, Weisan Chen, Gang Guo, Quan-Ming Zou, Yuan Zhuang
Natural killer (NK) cells are a major component of the host antitumor immune response in human cancer. However, the nature, functional regulation, and clinical relevance of NK cells in gastric cancer remain largely unknown. In this study, we showed that the percentages of NK cells in tumors were significantly decreased, and low percentages of tumor-infiltrating NK cells were positively correlated with poor survival and disease progression. Although the expression of activating and inhibitory receptors on NK cells was shown to be not different between tumor and nontumor tissues, NK cells in tumors had impaired effector functions, characterized by decreased IFNγ, TNFα, and Ki-67 expression...
February 1, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28108630/macropinocytosis-of-nab-paclitaxel-drives-macrophage-activation-in-pancreatic-cancer
#10
Jane Cullis, Despina Siolas, Antonina Avanzi, Sugata Barui, Anirban Maitra, Dafna Bar-Sagi
Pancreatic cancer is a devastating disease that is largely refractory to currently available treatment strategies. Therapeutic resistance is partially attributed to the dense stromal reaction of pancreatic ductal adenocarcinoma tumors that includes a pervasive infiltration of immunosuppressive (M2) macrophages. Nab-paclitaxel (trade name Abraxane) is a nanoparticle albumin-bound formulation of paclitaxel that, in combination with gemcitabine, is currently the first-line treatment for pancreatic cancer. Here, we show that macrophages internalized nab-paclitaxel via macropinocytosis...
January 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28093446/tumor-infiltrating-merkel-cell-polyomavirus-specific-t-cells-are-diverse-and-associated-with-improved-patient-survival
#11
Natalie J Miller, Candice D Church, Lichun Dong, David Crispin, Matthew P Fitzgibbon, Kristina Lachance, Lichen Jing, Michi Shinohara, Ioannis Gavvovidis, Gerald Willimsky, Martin McIntosh, Thomas Blankenstein, David M Koelle, Paul Nghiem
Tumor-infiltrating CD8(+) T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8(+) T-cell infiltration is robust in only 4% to 18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome. HLA-A*02:01/KLL tetramer(+) CD8(+) T cells from MCC patient peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) were isolated via flow cytometry...
January 16, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28250045/correction-deep-sequencing-of-t-cell-receptor-dna-as-a-biomarker-of-clonally-expanded-tils-in-breast-cancer-after-immunotherapy
#12
(no author information available yet)
No abstract text is available yet for this article.
March 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28250044/article-recommendations-from-our-deputy-and-senior-editors
#13
(no author information available yet)
No abstract text is available yet for this article.
March 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28143806/efficient-eradication-of-established-tumors-in-mice-with-cationic-liposome-based-synthetic-long-peptide-vaccines
#14
Eleni Maria Varypataki, Naomi Benne, Joke Bouwstra, Wim Jiskoot, Ferry Ossendorp
Therapeutic vaccination with synthetic long peptides (SLP) can be clinically effective against HPV-induced premalignant lesions; however, their efficiency in established malignant lesions leaves room for improvement. Here, we report the high therapeutic potency of cationic liposomes loaded with well-defined tumor-specific SLPs and a TLR3 ligand as adjuvant. The cationic particles, with an average size of 160 nm, could strongly activate functional, antigen-specific CD8(+) and CD4(+) T cells and induced in vivo cytotoxicity against target cells after intradermal vaccination...
March 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28137717/differentiated-state-of-initiating-tumor-cells-is-key-to-distinctive-immune-responses-seen-in-h-ras-g12v-induced-squamous-tumors
#15
Michael A Podolsky, Jacob T Bailey, Andrew J Gunderson, Carrie J Oakes, Kyle Breech, Adam B Glick
Heterogeneity in tumor immune responses is a poorly understood yet critical parameter for successful immunotherapy. In two doxycycline-inducible models where oncogenic H-Ras(G12V) is targeted either to the epidermal basal/stem cell layer with a Keratin14-rtTA transgene (K14Ras), or committed progenitor/suprabasal cells with an Involucrin-tTA transgene (InvRas), we observed strikingly distinct tumor immune responses. On threshold doxycycline levels yielding similar Ras expression, tumor latency, and numbers, tumors from K14Ras mice had an immunosuppressed microenvironment, whereas InvRas tumors had a proinflammatory microenvironment...
March 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28115358/therapeutic-efficacy-of-4-1bb-costimulation-is-abrogated-by-pd-1-blockade-in-a-model-of-spontaneous-b-cell-lymphoma
#16
Sara J McKee, Brianna L Doff, Megan S F Soon, Stephen R Mattarollo
Combinations of mAbs that target various components of T-cell activation/inhibition may work synergistically to improve antitumor immunity against cancer. In this study, we investigated the therapeutic potential of combining an anticancer vaccination strategy with antibodies targeting an immune stimulatory (4-1BB) and immune inhibitory (PD-1) receptor, in a preclinical model of spontaneously arising c-Myc-driven B-cell lymphoma. In Eμ-myc transgenic mice, we reveal that 4-1BB agonistic mAb treatment alone was sufficient to drive antitumor immunity and prevent disease progression in 70% of mice...
March 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28108629/myeloid-stat3-promotes-lung-tumorigenesis-by-transforming-tumor-immunosurveillance-into-tumor-promoting-inflammation
#17
Jingjiao Zhou, Zhaoxia Qu, Fan Sun, Lei Han, Liwen Li, Shapei Yan, Laura P Stabile, Lin-Feng Chen, Jill M Siegfried, Gutian Xiao
One of the most fundamental and challenging questions in the cancer field is how immunity in patients with cancer is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identify the transcription factor STAT3 as the culprit responsible for this pathogenic event in lung cancer development. We found that antitumor type 1 CD4(+) T-helper (Th1) cells and CD8(+) T cells were directly counter balanced in lung cancer development with tumor-promoting myeloid-derived suppressor cells (MDSCs) and suppressive macrophages, and that activation of STAT3 in MDSCs and macrophages promoted tumorigenesis through pulmonary recruitment and increased resistance of suppressive cells to CD8(+) T cells, enhancement of cytotoxicity toward CD4(+) and CD8(+) T cells, induction of regulatory T cell (Treg), inhibition of dendritic cells (DC), and polarization of macrophages toward the M2 phenotype...
March 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28148561/article-recommendations-from-our-deputy-and-senior-editors
#18
(no author information available yet)
No abstract text is available yet for this article.
February 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28093447/inflammasomes-and-cancer
#19
Rajendra Karki, Si Ming Man, Thirumala-Devi Kanneganti
Inflammation affects all stages of tumorigenesis. A key signaling pathway leading to acute and chronic inflammation is through activation of the caspase-1 inflammasome. Inflammasome complexes are assembled on activation of certain nucleotide-binding domain, leucine-rich repeat-containing proteins (NLR), AIM2-like receptors, or pyrin. Of these, NLRP1, NLRP3, NLRC4, NLRP6, and AIM2 influence the pathogenesis of cancer by modulating innate and adaptive immune responses, cell death, proliferation, and/or the gut microbiota...
February 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28077434/transfer-of-allogeneic-cd4-t-cells-rescues-cd8-t-cells-in-anti-pd-l1-resistant-tumors-leading-to-tumor-eradication
#20
Ainhoa Arina, Theodore Karrison, Eva Galka, Karin Schreiber, Ralph R Weichselbaum, Hans Schreiber
Adoptively transferred CD8(+) T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T-cell-mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule K(b) needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8(+) T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months...
February 2017: Cancer Immunology Research
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