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Cancer Immunology Research

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https://www.readbyqxmd.com/read/27737878/classical-hodgkin-lymphoma-with-reduced-%C3%AE-2m-mhc-class-i-expression-is-associated-with-inferior-outcome-independent-of-9p24-1-status
#1
Margaretha G M Roemer, Ranjana H Advani, Robert A Redd, Geraldine S Pinkus, Yasodha Natkunam, Azra H Ligon, Courtney F Connelly, Christine J Pak, Christopher D Carey, Sarah E Daadi, Bjoern Chapuy, Daphne de Jong, Richard T Hoppe, Donna S Neuberg, Margaret A Shipp, Scott J Rodig
In classical Hodgkin Lymphoma (cHL), malignant Hodgkin Reed-Sternberg (HRS) cells evade antitumor immunity by multiple mechanisms, including perturbed antigen presentation and enhanced PD-1 signaling. HRS cell expression of the PD-1 ligands is attributable, in part, to copy number alterations of 9p24.1/CD274(PD-L1)/PDCD1LG2(PD-L2) Amplification of PD-L1/PD-L2 is associated with advanced clinical stage and inferior progression-free survival (PFS) following frontline (induction) therapy. The relationships between altered expression of β2-microglobulin (β2M), MHC class I, and MHC class II by HRS cells, PD-L1/PD-L2 amplification, and clinical outcome in cHL are poorly defined...
October 13, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27697858/il-2-variant-circumvents-icos-regulatory-t-cell-expansion-and-promotes-nk-cell-activation
#2
Geok Choo Sim, Chengwen Liu, Ena Wang, Hui Liu, Caitlin Creasy, Zhimin Dai, Willem W Overwijk, Jason Roszik, Francesco M Marincola, Patrick Hwu, Elizabeth A Grimm, Laszlo G Radvanyi
Clinical responses to high-dose IL-2 therapy are limited due to selective expansion of CD4+CD25+oxp3+ T-regulatory cells (Tregs) especially ICOS+Tregs, rather than NK cells and effector T cells. These ICOS+Tregs are highly suppressive and constitutively express high levels of IL-2Ralpha (CD25) and CD39. Here, we characterized the effect of a mutant form of IL-2 (F42K), which preferentially binds to the lower affinity IL-2Rbetagamma with reduced binding to CD25, on Tregs, effector NK cells, and T-cell subsets...
October 3, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27638841/restoring-retinoic-acid-attenuates-intestinal-inflammation-and-tumorigenesis-in-apcmin-mice
#3
Hweixian Leong Penny, Tyler R Prestwood, Nupur Bhattacharya, Fionna Sun, Justin A Kenkel, Matthew G Davidson, Lei Shen, Luis A Zuniga, E Scott Seeley, Reetesh Pai, Okmi Choi, Lorna Tolentino, Jinshan Wang, Joseph L Napoli, Edgar G Engleman
Chronic intestinal inflammation accompanies familial adenomatous polyposis (FAP) and is a major risk factor for colorectal cancer in patients with this disease, but the cause of such inflammation is unknown. Because retinoic acid (RA) plays a critical role in maintaining immune homeostasis in the intestine, we hypothesized that altered RA metabolism contributes to inflammation and tumorigenesis in FAP. To assess this hypothesis, we analyzed RA metabolism in the intestines of patients with FAP as well as APC(Min/+) mice, a model that recapitulates FAP in most respects...
September 16, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27908932/acknowledgment-to-reviewers
#4
(no author information available yet)
No abstract text is available yet for this article.
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27908931/filling-the-tank-keeping-antitumor-t-cells-metabolically-fit-for-the-long-haul
#5
REVIEW
Greg M Delgoffe
Discoveries in tumor immunology and subsequent clinical advances in cancer immunotherapy have revealed that the immune system is not oblivious to tumor progression but heavily interacts with developing neoplasia and malignancy. A major factor preventing immune destruction is the establishment of a highly immunosuppressive tumor microenvironment (TME), which provides architecture to the tumor, supports indirect means of immunosuppression such as the recruitment of tolerogenic cells like regulatory T cells and myeloid-derived suppressor cells (MDSC), and represents a zone of metabolically dearth conditions...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27908930/translating-science-into-survival-report-on-the-second-international-cancer-immunotherapy-conference
#6
Arthur N Brodsky, Vanessa M Hubbard-Lucey
On September 25-28, 2016, in New York City, the Second International Cancer Immunotherapy Conference was cohosted by the Cancer Research Institute, the American Association for Cancer Research, the Association for Cancer Immunotherapy, and the European Academy of Tumor Immunology. This exciting conference brought together more than 1,400 participants, including scientists, clinicians, investors, and regulators, to discuss the latest scientific advances within the field of cancer immunotherapy. This conference report reviews the chief themes that emerged during the 4-day meeting...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27908929/article-recommendations-from-our-deputy-and-senior-editors
#7
(no author information available yet)
No abstract text is available yet for this article.
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27856426/cytotoxic-t-cells-in-pd-l1-positive-malignant-pleural-mesotheliomas-are-counterbalanced-by-distinct-immunosuppressive-factors
#8
Mark M Awad, Robert E Jones, Hongye Liu, Patrick H Lizotte, Elena V Ivanova, Meghana Kulkarni, Grit S Herter-Sprie, Xiaoyun Liao, Abigail A Santos, Mark A Bittinger, Lauren Keogh, Shohei Koyama, Christina Almonte, Jessie M English, Julianne Barlow, William G Richards, David A Barbie, Adam J Bass, Scott J Rodig, F Stephen Hodi, Kai W Wucherpfennig, Pasi A Jänne, Lynette M Sholl, Peter S Hammerman, Kwok-Kin Wong, Raphael Bueno
PD-L1 immunohistochemical staining does not always predict whether a cancer will respond to treatment with PD-1 inhibitors. We sought to characterize immune cell infiltrates and the expression of T-cell inhibitor markers in PD-L1-positive and PD-L1-negative malignant pleural mesothelioma samples. We developed a method for immune cell phenotyping using flow cytometry on solid tumors that have been dissociated into single-cell suspensions and applied this technique to analyze 43 resected malignant pleural mesothelioma specimens...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27856425/pd-1-suppresses-development-of-humoral-responses-that-protect-against-tn-bearing-tumors
#9
Marcela A Haro, Chad A Littrell, Zhaojun Yin, Xuefei Huang, Karen M Haas
Tn is a carbohydrate antigen uniquely exposed on tumor mucins and, thus, an ideal target for immunotherapy. However, it has been difficult to elicit protective antibody responses against Tn antigen and other tumor-associated carbohydrate antigens. Our study demonstrates this can be attributed to PD-1 immuno-inhibition. Our data show a major role for PD-1 in suppressing mucin- and Tn-specific B-cell activation, expansion, and antibody production important for protection against Tn-bearing tumor cells. These Tn/mucin-specific B cells belong to the innate-like B-1b cell subset typically responsible for T cell-independent antibody responses...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27856424/eradication-of-canine-diffuse-large-b-cell-lymphoma-in-a-murine-xenograft-model-with-cd47-blockade-and-anti-cd20
#10
Kipp Weiskopf, Katie L Anderson, Daisuke Ito, Peter J Schnorr, Hirotaka Tomiyasu, Aaron M Ring, Kristin Bloink, Jem Efe, Sarah Rue, David Lowery, Amira Barkal, Susan Prohaska, Kelly M McKenna, Ingrid Cornax, Timothy D O'Brien, M Gerard O'Sullivan, Irving L Weissman, Jaime F Modiano
Cancer immunotherapies hold much promise, but their potential in veterinary settings has not yet been fully appreciated. Canine lymphomas are among the most common tumors of dogs and bear remarkable similarity to human disease. In this study, we examined the combination of CD47 blockade with anti-CD20 passive immunotherapy for canine lymphoma. The CD47/SIRPα axis is an immune checkpoint that regulates macrophage activation. In humans, CD47 is expressed on cancer cells and enables evasion from phagocytosis...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27821498/established-t-cell-inflamed-tumors-rejected-after-adaptive-resistance-was-reversed-by-combination-sting-activation-and-pd-1-pathway-blockade
#11
Ellen Moore, Paul E Clavijo, Ruth Davis, Harrison Cash, Carter Van Waes, Young Kim, Clint Allen
Patients with head and neck squamous cell carcinoma harbor T cell-inflamed and non-T cell-inflamed tumors. Despite this, only 20% of patients respond to checkpoint inhibitor immunotherapy. Lack of induction of innate immunity through pattern-recognition receptors, such as the stimulator of interferon (IFN) genes (STING) receptor, may represent a significant barrier to the development of effective antitumor immunity. Here, we demonstrate robust control of a T cell-inflamed (MOC1), but not non-T cell-inflamed (MOC2), model of head and neck cancer by activation of the STING pathway with the synthetic cyclic dinucleotide RP,RP dithio-c-di-GMP...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27803062/rescue-of-tolerant-cd8-t-cells-during-cancer-immunotherapy-with-il2-antibody-complexes
#12
Lauryn E Klevorn, Melissa M Berrien-Elliott, Jinyun Yuan, Lindsey M Kuehm, Gregory D Felock, Sean A Crowe, Ryan M Teague
Interleukin-2 (IL2) was among the earliest reagents used for cancer immunotherapy due to its ability to support the survival and function of tumor-reactive T cells. However, treatment with IL2 is accompanied by off-target toxicity and low response rates in patients. In mouse models, these issues are largely overcome when IL2 is administered as a cytokine/antibody complex (IL2c). The complex has a longer serum half-life and can be designed for preferential cytokine delivery to specific cells of interest. Early studies showed IL2c could boost antitumor immunity in mice by activating tumor-reactive CD8(+) T cells...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27799141/survival-of-lung-adenocarcinoma-patients-predicted-from-expression-of-pd-l1-galectin-9-and-xage1-gaged2a-on-tumor-cells-and-tumor-infiltrating-t-cells
#13
Yoshihiro Ohue, Koji Kurose, Ryohei Nozawa, Midori Isobe, Yumi Nishio, Tomonori Tanaka, Yoshinori Doki, Takashi Hori, Junya Fukuoka, Mikio Oka, Eiichi Nakayama
The immune status of tumors varies, and this may affect the overall survival (OS) of patients. We examined tumors from 120 patients with lung adenocarcinomas with a tissue microarray for T-cell infiltration and the expression of PD-L1 and Galectin-9 (both ligands for inhibitory receptors on T cells), and cancer/testis (CT) antigen XAGE1 (GAGED2a; a tumor antigen often found on lung tumors) expression, to determine their relevance to OS. Patients defined as pStage I-IIIA could be grouped, based on the expression profiles of PD-L1, Galectin-9, and XAGE1, into cluster A, who had prolonged survival, and cluster B, who had shorter survival...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27799140/endogenous-neoantigen-specific-cd8-t-cells-identified-in-two-glioblastoma-models-using-a-cancer-immunogenomics-approach
#14
Tanner M Johanns, Jeffrey P Ward, Christopher A Miller, Courtney Wilson, Dale K Kobayashi, Diane Bender, Yujie Fu, Anton Alexandrov, Elaine R Mardis, Maxim N Artyomov, Robert D Schreiber, Gavin P Dunn
The "cancer immunogenomics" paradigm has facilitated the search for tumor-specific antigens over the last 4 years by applying comprehensive cancer genomics to tumor antigen discovery. We applied this methodology to identify tumor-specific "neoantigens" in the C57BL/6-derived GL261 and VM/Dk-derived SMA-560 tumor models. Following DNA whole-exome and RNA sequencing, high-affinity candidate neoepitopes were predicted and screened for immunogenicity by ELISPOT and tetramer analyses. GL261 and SMA-560 harbored 4,932 and 2,171 nonsynonymous exome mutations, respectively, of which less than half were expressed...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27803050/immunological-mechanisms-underneath-the-efficacy-of-cancer-therapy
#15
REVIEW
Lorenzo Galluzzi, Laurence Zitvogel, Guido Kroemer
Accumulating preclinical and clinical evidence indicates that the success of several anticancer agents-including some conventional chemotherapeutics, targeted anticancer agents as well as specific forms of radiotherapy-depends (at least in part) on their ability to stimulate anticancer immune responses. Such immunostimulatory effects can be "on-target," i.e., they originate within cancer cells, or "off-target," i.e., they develop from a heretofore unsuspected interaction between cancer therapy and the immune system...
November 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27803049/about-the-masters
#16
REVIEW
(no author information available yet)
No abstract text is available yet for this article.
November 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27803048/article-recommendations-from-our-deputy-and-senior-editors
#17
(no author information available yet)
No abstract text is available yet for this article.
November 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27737879/cxcr2-dependent-accumulation-of-tumor-associated-neutrophils-regulates-t-cell-immunity-in-pancreatic-ductal-adenocarcinoma
#18
Timothy Chao, Emma E Furth, Robert H Vonderheide
Tumor-associated neutrophils are increasingly recognized for their ability to promote tumor progression, mediate resistance to therapy, and regulate immunosuppression. Evidence from various murine models has shown that the chemokine receptor CXCR2 attracts neutrophil into tumors and, therefore, represents a tractable therapeutic target. Here, we report prominent expression of a neutrophil gene signature in a subset of human pancreatic adenocarcinoma (PDA). CXCL5 was the most prominently expressed CXCR2 ligand in human PDA, and its expression was higher in PDA than in any other common tumor represented in The Cancer Genome Atlas...
November 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27737877/microrna-let-7-t-cells-and-patient-survival-in-colorectal-cancer
#19
Ruoxu Dou, Reiko Nishihara, Yin Cao, Tsuyoshi Hamada, Kosuke Mima, Atsuhiro Masuda, Yohei Masugi, Yan Shi, Mancang Gu, Wanwan Li, Annacarolina da Silva, Katsuhiko Nosho, Xuehong Zhang, Jeffrey A Meyerhardt, Edward L Giovannucci, Andrew T Chan, Charles S Fuchs, Zhi Rong Qian, Shuji Ogino
Experimental evidence suggests that the let-7 family of noncoding RNAs suppresses adaptive immune responses, contributing to immune evasion by the tumor. We hypothesized that the amount of let-7a and let-7b expression in colorectal carcinoma might be associated with limited T-lymphocyte infiltrates in the tumor microenvironment and worse clinical outcome. Utilizing the molecular pathological epidemiology resources of 795 rectal and colon cancers in two U.S.-nationwide prospective cohort studies, we measured tumor-associated let-7a and let-7b expression levels by quantitative reverse-transcription PCR, and CD3(+), CD8(+), CD45RO (PTPRC)(+), and FOXP3(+) cell densities by tumor tissue microarray immunohistochemistry and computer-assisted image analysis...
November 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27688020/systemic-gm-csf-recruits-effector-t-cells-into-the-tumor-microenvironment-in-localized-prostate-cancer
#20
Xiao X Wei, Stephen Chan, Serena Kwek, Jera Lewis, Vinh Dao, Li Zhang, Matthew R Cooperberg, Charles J Ryan, Amy M Lin, Terence W Friedlander, Brian Rini, Christopher Kane, Jeffry P Simko, Peter R Carroll, Eric J Small, Lawrence Fong
Granulocytic-macrophage colony-stimulating factor (GM-CSF) is used as an adjuvant in cancer vaccine trials and has the potential to enhance antitumor efficacy with immunotherapy; however, its immunologic effects are not fully understood. Here, we report results from a phase I study of neoadjuvant GM-CSF in patients with localized prostate cancer undergoing radical prostatectomy. Patients received subcutaneous injections of GM-CSF (250 μg/m(2)/day) daily for 2 weeks (cohort 1; n = 6), 3 weeks (cohort 2; n = 6), or 4 weeks (cohort 3; n = 6)...
November 2016: Cancer Immunology Research
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