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Journal for Immunotherapy of Cancer

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https://read.qxmd.com/read/30777137/acute-liver-injury-in-the-context-of-immune-checkpoint-inhibitor-related-colitis-treated-with-infliximab
#1
Hao Chi Zhang, Wenyi Luo, Yinghong Wang
BACKGROUND: Immune checkpoint inhibitors (ICPIs), used to treat different advanced malignancies, are associated with a wide range of immune-related adverse reactions (irAEs) that deserve close monitoring of patients. Gastrointestinal reactions and hepatotoxicity may occur, which warrant careful evaluation to confirm the etiology and attribution to ICPIs as these events could affect future management. CASE PRESENTATION: We describe a case of a patient with prostate adenocarcinoma, treated with dual ICPIs comprised of ipilimumab and nivolumab, who developed elevated liver enzymes in the context of infliximab therapy prescribed to treat gastrointestinal irAE from his ICPIs...
February 18, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30777131/therapy-with-high-dose-interleukin-2-hd-il-2-in-metastatic-melanoma-and-renal-cell-carcinoma-following-pd1-or-pdl1-inhibition
#2
Elizabeth I Buchbinder, Janice P Dutcher, Gregory A Daniels, Brendan D Curti, Sapna P Patel, Shernan G Holtan, Gerald P Miletello, Mayer N Fishman, Rene Gonzalez, Joseph I Clark, John M Richart, Christopher D Lao, Scott S Tykodi, Ann W Silk, David F McDermott
BACKGROUND: Metastatic melanoma (mM) and renal cell carcinoma (mRCC) are often treated with anti-PD-1 based therapy, however not all patients respond and further therapies are needed. High dose interleukin-2 (HD IL-2) can lead to durable responses in a subset of mM and mRCC patients. The efficacy and toxicity of HD IL-2 therapy following anti-PD-1 or anti-PD-L1 therapy have not yet been explored. METHODS: Reports on mM and mRCC patients who had received HD IL-2 after PD-1 or PD-L1 inhibition were queried from the PROCLAIMSM database...
February 18, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30777125/nkg2d-signaling-certifies-effector-cd8-t-cells-for-memory-formation
#3
Cynthia Perez, Kushal Prajapati, Brianna Burke, Lourdes Plaza-Rojas, Nancy J Zeleznik-Le, Jose A Guevara-Patino
BACKGROUND: The development of memory responses is an evolutionary function of the adaptive immune system. We propose that for the immune system to populate the memory compartment with the best-suited CD8 T cells it utilizes a process of certification or molecular accreditation mediated through Natural Killer Group 2D (NKG2D). This process of certification assures that the memory compartment is filled with CD8 T cells that have demonstrated their ability to kill their cognate targets through a two-step process that utilizes T cell receptor (TCR) and NKG2D signaling...
February 18, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30760333/the-il-1-il-1-receptor-axis-and-tumor-cell-released-inflammasome-adaptor-asc-are-key-regulators-of-tslp-secretion-by-cancer-associated-fibroblasts-in-pancreatic-cancer
#4
Emanuela Brunetto, Lucia De Monte, Gianpaolo Balzano, Barbara Camisa, Vincenzo Laino, Michela Riba, Silvia Heltai, Marco Bianchi, Claudio Bordignon, Massimo Falconi, Attilio Bondanza, Claudio Doglioni, Maria Pia Protti
BACKGROUND: The thymic stromal lymphopoietin (TSLP), a key cytokine for development of Th2 immunity, is produced by cancer associated fibroblasts (CAFs) in pancreatic cancer where predominant tumor infiltrating Th2 over Th1 cells correlates with reduced patients' survival. Which cells and molecules are mostly relevant in driving TSLP secretion by CAFs in pancreatic cancer is not defined. METHODS: We performed in vitro, in vivo and ex-vivo analyses. For in vitro studies we used pancreatic cancer cell lines, primary CAFs cultures, and THP1 cells...
February 13, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30760319/correction-to-33rd-annual-meeting-pre-conference-programs-of-the-society-for-immunotherapy-of-cancer-sitc-2018
#5
Sneha Berry, Nicolas Giraldo, Peter Nguyen, Benjamin Green, Haiying Xu, Aleksandra Ogurtsova, Abha Soni, Farah Succaria, Daphne Wang, Charles Roberts, Julie Stein, Elizabeth Engle, Drew Pardoll, Robert Anders, Tricia Cottrell, Janis M Taube, Ben Tran, Mark Voskoboynik, James Kuo, Yung-Lue Bang, Hyun-Cheo Chung, Myung-Ju Ahn, Sang-We Kim, Ayesh Perera, Daniel Freeman, Ikbel Achour, Raffaella Faggioni, Feng Xiao, Charles Ferte, Charlotte Lemech, Funda Meric-Bernstam, Theresa Werner, Stephen Hodi, Wells Messersmith, Nancy Lewis, Craig Talluto, Mirek Dostalek, Aiyang Tao, Sarah McWhirter, Damian Trujillo, Jason Luke, Chunxiao Xu, BoMarelli, Jin Qi, Guozhong Qin, Huakui Yu, Molly Jenkins, Kin-Ming Lo, Joern-Peter Halle, Yan Lan, Matthew Taylor, Nicholas Vogelzang, Allen Cohn, Daniel Stepan, Robert Shumaker, Corina Dutcus, Matthew Guo, Emmett Schmidt, Drew Rasco, Marcia Brose, Nicholas Vogelzang, Christopher Di Simone, Sharad Jain, Donald Richards, Carlos Encarnacion, Drew Rasco, Robert Shumaker, Corina Dutcus, Daniel Stepan, Matthew Guo, Emmett Schmidt, Matthew Taylor, Nicholas Vogelzang, Carlos Encarnacion, Allen Cohn, Christopher Di Simone, Drew Rasco, Donald Richards, Matthew Taylor, Corina Dutcus, Daniel Stepan, Robert Shumaker, Matthew Guo, Emmett Schmidt, James Mier, Jeongshin An, Yeun-Yeoul Yang, Won-Hee Lee, Jinho Yang, Jong-Kyu Kim, Hyun Goo Kim, Se Hyun Paek, Jun Woo Lee, Joohyun Woo, Jong Bin Kim, Hyungju Kwon, Woosung Lim, Nam Sun Paik, Yoon-Keun Kim, Byung-In Moon, Filip Janku, David Tan, Juan Martin-Liberal, Shunji Takahashi, Ravit Geva, Ayca Gucalp, Xueying Chen, Kulandayan Subramanian, Jennifer Mataraza, Jennifer Wheler, Philippe Bedard
After publication of this supplement [1, 2], it was brought to our attention that due to an error authors were missing in the following abstracts. This has now been included in this correction.
February 13, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30755279/efficacy-of-pd-1-blockade-in-cervical-cancer-is-related-to-a-cd8-foxp3-cd25-t-cell-subset-with-operational-effector-functions-despite-high-immune-checkpoint-levels
#6
A M Heeren, J Rotman, A G M Stam, N Pocorni, A A Gassama, S Samuels, M C G Bleeker, C H Mom, H J M A A Zijlmans, G G Kenter, E S Jordanova, T D de Gruijl
BACKGROUND: Cervical cancer (CxCa) is mainly a locally invading disease that metastasizes to loco-regional lymph node basins before involving distant organs in more advanced stages. Local immune potentiation of tumor-draining lymph nodes (TDLN) may thus protect against tumor progression. METHODS: To identify therapeutic targets for local immune modulation, multi-parameter flow cytometric T-cell profiling of primary cervical tumors (PT) and TDLN (n = 37) was performed...
February 12, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30755273/the-motility-regulator-flhdc-drives-intracellular-accumulation-and-tumor-colonization-of-salmonella
#7
Vishnu Raman, Nele Van Dessel, Owen M O'Connor, Neil S Forbes
BACKGROUND: Salmonella have potential as anticancer therapeutic because of their innate tumor specificity. In clinical studies, this specificity has been hampered by heterogeneous responses. Understanding the mechanisms that control tumor colonization would enable the design of more robust therapeutic strains. Two mechanisms that could affect tumor colonization are intracellular accumulation and intratumoral motility. Both of these mechanisms have elements that are controlled by the master motility regulator flhDC...
February 12, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30744698/antitumor-response-to-microscopic-melanoma-in-the-gastric-mucosa-mimicking-ipilimumab-induced-gastritis
#8
Elisa Bello, Justine V Cohen, Mari Mino-Kenudson, Michael Dougan
BACKGROUND: Alongside its clinical success, checkpoint blockade has also given rise to a set of immune-related adverse events (irAEs). In addition to causing considerable morbidity and even mortality, irAEs may limit the success and scope of immunotherapy. Most irAEs arise at mucosal barriers, including the gastrointestinal mucosa, leading most commonly to colitis, though both gastritis and enteritis can result from checkpoint blockade. While guidelines generally recommend confirmatory testing for suspected severe irAEs, the role of endoscopy in diagnosing more moderate irAEs is less clear...
February 11, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30744692/persistent-mutant-oncogene-specific-t-cells-in-two-patients-benefitting-from-anti-pd-1
#9
Kellie N Smith, Nicolas J Llosa, Tricia R Cottrell, Nicholas Siegel, Hongni Fan, Prerna Suri, Hok Yee Chan, Haidan Guo, Teniola Oke, Anas H Awan, Franco Verde, Ludmila Danilova, Valsamo Anagnostou, Ada J Tam, Brandon S Luber, Bjarne R Bartlett, Laveet K Aulakh, John-William Sidhom, Qingfeng Zhu, Cynthia L Sears, Leslie Cope, William H Sharfman, Elizabeth D Thompson, Joanne Riemer, Kristen A Marrone, Jarushka Naidoo, Victor E Velculescu, Patrick M Forde, Bert Vogelstein, Kenneth W Kinzler, Nickolas Papadopoulos, Jennifer N Durham, Hao Wang, Dung T Le, Sune Justesen, Janis M Taube, Luis A Diaz, Julie R Brahmer, Drew M Pardoll, Robert A Anders, Franck Housseau
BACKGROUND: Several predictive biomarkers are currently approved or are under investigation for the selection of patients for checkpoint blockade. Tumor PD-L1 expression is used for stratification of non-small cell lung (NSCLC) patients, with tumor mutational burden (TMB) also being explored with promising results, and mismatch-repair deficiency is approved for tumor site-agnostic disease. While tumors with high PD-L1 expression, high TMB, or mismatch repair deficiency respond well to checkpoint blockade, tumors with lower PD-L1 expression, lower mutational burdens, or mismatch repair proficiency respond much less frequently...
February 11, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30744691/cancer-cell-secreted-cxcl11-promoted-cd8-t-cells-infiltration-through-docetaxel-induced-release-of-hmgb1-in-nsclc
#10
Qun Gao, Shumin Wang, Xinfeng Chen, Shaoyan Cheng, Zhen Zhang, Feng Li, Lan Huang, Yang Yang, Bin Zhou, Dongli Yue, Dan Wang, Ling Cao, Nomathamsanqa Resegofetse Maimela, Bin Zhang, Jane Yu, Liping Wang, Yi Zhang
BACKGROUND: Chemotherapy combined with immunotherapy becomes the main trend in lung cancer intervention; however, how chemotherapy promotes the immune function remains elusive. Therefore, we sought to determine how chemotherapy promotes the immune function. METHODS: We determined in 100 NSCLC patients the expression of CD8, functional markers (IFN-γ, Granzyme B, and Perforin) and specific chemokines by quantitative real-time reverse transcriptase-PCR. Functional experiments were carried out to check whether docetaxel (DOC), a chemotherapeutic agent, modifies the expression of HMGB1 and CXCL11, and influences the infiltration properties of CD8+ T cells to the tumor microenvironment...
February 11, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30736858/are-tumor-size-changes-predictive-of-survival-for-checkpoint-blockade-based-immunotherapy-in-metastatic-melanoma
#11
Meihua Wang, Cong Chen, Thomas Jemielita, James Anderson, Xiaoyun Nicole Li, Chen Hu, S Peter Kang, Nageatte Ibrahim, Scot Ebbinghaus
BACKGROUND: In oncology clinical development, objective response rate, disease control rate and early tumor size changes are commonly used as efficacy metrics for early decision-making. However, for immunotherapy trials, it is unclear whether these early efficacy metrics are still predictive of long-term clinical benefit such as overall survival. The goal of this paper is to identify appropriate early efficacy metrics predictive of overall survival for immunotherapy trials. METHODS: Based on several checkpoint blockade based immunotherapy studies in metastatic melanoma, we evaluated the predictive value of early tumor size changes and RECIST-based efficacy metrics at various time points on overall survival...
February 8, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30736857/characterization-of-immune-responses-to-anti-pd-1-mono-and-combination-immunotherapy-in-hematopoietic-humanized-mice-implanted-with-tumor-xenografts
#12
A Capasso, J Lang, T M Pitts, K R Jordan, C H Lieu, S L Davis, J R Diamond, S Kopetz, J Barbee, J Peterson, B M Freed, B W Yacob, S M Bagby, W A Messersmith, J E Slansky, R Pelanda, S G Eckhardt
BACKGROUND: The success of agents that reverse T-cell inhibitory signals, such as anti-PD-1/PD-L1 therapies, has reinvigorated cancer immunotherapy research. However, since only a minority of patients respond to single-agent therapies, methods to test the potential anti-tumor activity of rational combination therapies are still needed. Conventional murine xenograft models have been hampered by their immune-compromised status; thus, we developed a hematopoietic humanized mouse model, hu-CB-BRGS, and used it to study anti-tumor human immune responses to triple-negative breast cancer (TNBC) cell line and patient-derived colorectal cancer (CRC) xenografts (PDX)...
February 8, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30736852/allogenic-v%C3%AE-9v%C3%AE-2-t-cell-as-new-potential-immunotherapy-drug-for-solid-tumor-a-case-study-for-cholangiocarcinoma
#13
Mohammed Alnaggar, Yan Xu, Jingxia Li, Junyi He, Jibing Chen, Man Li, Qingling Wu, Li Lin, Yingqing Liang, Xiaohua Wang, Jiawei Li, Yi Hu, Yan Chen, Kecheng Xu, Yangzhe Wu, Zhinan Yin
BACKGROUND: Cholangiocarcinoma (CCA) is a highly aggressive and fatal tumor. CCA occurs in the epithelial cells of bile ducts. Due to increasing incidences, CCA accounts for 3% of all gastrointestinal malignancies. In addition to comprehensive treatments for cancer, such as surgery, chemotherapy, and radiotherapy, during the past few years, cellular immunotherapy has played an increasingly important role. As a result of our research, we have discovered the γδ T cell-based immunotherapy for CCA...
February 8, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30736848/phase-ib-evaluation-of-a-self-adjuvanted-protamine-formulated-mrna-based-active-cancer-immunotherapy-bi1361849-cv9202-combined-with-local-radiation-treatment-in-patients-with-stage-iv-non-small-cell-lung-cancer
#14
Alexandros Papachristofilou, Madeleine M Hipp, Ute Klinkhardt, Martin Früh, Martin Sebastian, Christian Weiss, Miklos Pless, Richard Cathomas, Wolfgang Hilbe, Georg Pall, Thomas Wehler, Jürgen Alt, Helge Bischoff, Michael Geißler, Frank Griesinger, Karl-Josef Kallen, Mariola Fotin-Mleczek, Andreas Schröder, Birgit Scheel, Anke Muth, Tobias Seibel, Claudia Stosnach, Fatma Doener, Henoch S Hong, Sven D Koch, Ulrike Gnad-Vogt, Alfred Zippelius
BACKGROUND: Preclinical studies demonstrate synergism between cancer immunotherapy and local radiation, enhancing anti-tumor effects and promoting immune responses. BI1361849 (CV9202) is an active cancer immunotherapeutic comprising protamine-formulated, sequence-optimized mRNA encoding six non-small cell lung cancer (NSCLC)-associated antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, and MUC-1), intended to induce targeted immune responses. METHODS: We describe a phase Ib clinical trial evaluating treatment with BI1361849 combined with local radiation in 26 stage IV NSCLC patients with partial response (PR)/stable disease (SD) after standard first-line therapy...
February 8, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30732646/different-role-of-circulating-myeloid-derived-suppressor-cells-in-patients-with-multiple-myeloma-undergoing-autologous-stem-cell-transplantation
#15
Sung-Eun Lee, Ji-Young Lim, Tae Woo Kim, Da-Bin Ryu, Sung Soo Park, Young-Woo Jeon, Jae-Ho Yoon, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Seok Lee, Seok-Goo Cho, Dong-Wook Kim, Jong Wook Lee, Chang-Ki Min
BACKGROUND: The aim of this study is to evaluate the prognostic impact of myeloid-derived suppressor cells (MDSCs) in multiple myeloma (MM) in the context of autologous stem cell transplantation (ASCT). METHODS: Peripheral blood samples were collected for measuring monocytic (M-) MDSCs (CD14pos HLA-DRlow/neg ) and early-stage (E-) MDSCs (Linneg HLA-DRneg CD33pos CD11bpos ) before and after ASCT. Clinical outcomes following ASCT differed according to the frequency of each MDSC phenotype...
February 7, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30728081/prognostic-value-of-cd8-pd-1-immune-infiltrates-and-pdcd1-gene-expression-in-triple-negative-breast-cancer
#16
Joe Yeong, Jeffrey Chun Tatt Lim, Bernett Lee, Huihua Li, Clara Chong Hui Ong, Aye Aye Thike, Wei Hseun Yeap, Yi Yang, Ansel Yi Herh Lim, Timothy Kwang Yong Tay, Jin Liu, Siew-Cheng Wong, Jinmiao Chen, Elaine Hsuen Lim, Jabed Iqbal, Rebecca Dent, Evan W Newell, Puay Hoon Tan
The role of programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) in triple negative breast cancer (TNBC) remains to be fully understood. In this study, we investigated the role of PD-1 as a prognostic marker for TNBC in an Asian cohort (n = 269). Samples from patients with TNBC were labeled with antibodies against PD-L1 and PD-1, and subjected to NanoString assays to measure the expression of immune-related genes. Associations between disease-free survival (DFS), overall survival (OS) and biomarker expression were investigated...
February 6, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30728077/suppression-of-myeloid-cell-arginase-activity-leads-to-therapeutic-response-in-a-nsclc-mouse-model-by-activating-anti-tumor-immunity
#17
Juan J Miret, Paul Kirschmeier, Shohei Koyama, Mingrui Zhu, Yvonne Y Li, Yujiro Naito, Min Wu, Venkat S Malladi, Wei Huang, William Walker, Sangeetha Palakurthi, Glenn Dranoff, Peter S Hammerman, Chad V Pecot, Kwok-Kin Wong, Esra A Akbay
BACKGROUND: Tumor orchestrated metabolic changes in the microenvironment limit generation of anti-tumor immune responses. Availability of arginine, a semi-essential amino acid, is critical for lymphocyte proliferation and function. Levels of arginine are regulated by the enzymes arginase 1,2 and nitric oxide synthase (NOS). However, the role of arginase activity in lung tumor maintenance has not been investigated in clinically relevant orthotopic tumor models. METHODS: RNA sequencing (RNA-seq) of sorted cell populations from mouse lung adenocarcinomas derived from immunocompetent genetically engineered mouse models (GEMM)s was performed...
February 6, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30728076/clinical-characteristics-and-outcomes-of-immune-checkpoint-inhibitor-induced-pancreatic-injury
#18
Hamzah Abu-Sbeih, Tenglong Tang, Yang Lu, Selvi Thirumurthi, Mehmet Altan, Amir A Jazaeri, Ramona Dadu, Emmanuel Coronel, Yinghong Wang
BACKGROUND: Immune checkpoint inhibitor (ICI)-induced pancreatic injury (ICIPI) is not well documented in the literature. We aimed to describe the clinical characteristics and outcomes of patients who developed ICIPI. METHODS: We reviewed the medical records of consecutive patients who had a confirmed diagnosis of ICIPI (Common Terminology Criteria for Adverse Events grade ≥ 3 lipase elevation with or without clinical symptoms) from April 2011 through April 2018...
February 6, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30728070/hdac6-selective-inhibition-of-melanoma-patient-t-cells-augments-anti-tumor-characteristics
#19
Andressa S Laino, B C Betts, A Veerapathran, I Dolgalev, A Sarnaik, S N Quayle, S S Jones, J S Weber, David M Woods
BACKGROUND: Therapies targeting anti-tumor T-cell responses have proven successful in the treatment of a variety of malignancies. However, as most patients still fail to respond, approaches to augment immunotherapeutic efficacy are needed. Here, we investigated the ability of histone deacetylase 6 (HDAC6)-selective inhibitors to decrease immunosuppression and enhance immune function of melanoma patient T-cells in ex vivo cultures. METHODS: T-cells were harvested from peripheral blood or tumor biopsies of metastatic melanoma patients and cultured in the presence of pan-, class-specific or class-selective histone deacetylase (HDAC) inhibitors...
February 6, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30717817/tnf-%C3%AE-enhances-th9-cell-differentiation-and-antitumor-immunity-via-tnfr2-dependent-pathways
#20
Yuxue Jiang, Jintong Chen, Enguang Bi, Yinghua Zhao, Tianxue Qin, Yiming Wang, Alison Wang, Sujun Gao, Qing Yi, Siqing Wang
Tumor specific Th9 cells are potential effector cells for adoptive therapy of human cancers. TNF family members OX40L, TL1A and GITRL have been shown to promote the induction of Th9 cells and antitumor immunity. However, the role of TNF-α, the prototype of the TNF superfamily cytokines, in Th9 cell differentiation and their antitumor efficacy is not defined. Here, we showed that TNF-α potently promoted naïve CD4+ T cells to differentiate into Th9 cells in vitro. Furthermore, the addition of TNF-α during Th9 cell differentiation increased T cell survival and proliferation...
February 4, 2019: Journal for Immunotherapy of Cancer
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