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Cancer Immunology Research

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https://www.readbyqxmd.com/read/28411193/liver-metastasis-and-treatment-outcome-with-anti-pd-1-monoclonal-antibody-in-patients-with-melanoma-and-nsclc
#1
Paul C Tumeh, Matthew D Hellmann, Omid Hamid, Katy K Tsai, Kimberly L Loo, Matthew A Gubens, Michael Rosenblum, Christina L Harview, Janis Taube, Nathan Handley, Neharika Khurana, Adi Nosrati, Matthew F Krummel, Andrew Tucker, Eduardo Sosa, Philip J Sanchez, Nooriel Banayan, Juan Osorio, Dan L Nguyen-Kim, Jeremy Chang, I Peter Shintaku, Peter Boasberg, Emma J Taylor, Pamela N Munster, Alain P Algazi, Bartosz Chmielowski, Reinhard Dummer, Tristan R Grogan, David A Elashoff, Jimmy Hwang, Simone Goldinger, Edward Garon, Robert H Pierce, Adil I Daud
We explored the association between liver metastases, tumor CD8+ T cell count, and response in patients with melanoma or lung cancer treated with the anti-PD-1 antibody, pembrolizumab. The melanoma discovery cohort was drawn from the Phase I Keynote 001 trial, whereas the melanoma validation cohort was drawn from Keynote 002, 006, and EAP trials and the non-small cell lung cancer (NSCLC) cohort from Keynote 001. Liver metastasis was associated with reduced response and shortened progression-free survival (PFS); [objective response rate (ORR), 30...
April 14, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28408386/increased-pd-1-and-tim-3-tils-during-cetuximab-therapy-inversely-correlates-with-response-in-head-and-neck-cancer-patients
#2
Hyun-Bae Jie, Raghvendra M Srivastava, Athanassios Argiris, Julie E Bauman, Lawrence P Kane, Robert L Ferris
Despite emerging appreciation for the important role of immune checkpoint receptors in regulating the effector functions of T cells, it is unknown whether their expression is involved in determining the clinical outcome in response to cetuximab therapy. We examined the expression patterns of immune checkpoint receptors (including PD-1, CTLA-4, and TIM-3) and cytolytic molecules (including granzyme B and perforin) of CD8+ tumorinfiltrating lymphocytes (TILs) and compared them to those of peripheral blood T lymphocytes (PBLs) in patients with head and neck cancer (HNSCC) during cetuximab therapy...
April 13, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28396509/clinical-features-of-acquired-resistance-to-anti-pd-1-therapy-in-advanced-melanoma
#3
Daniel Y Wang, Zeynep Eroglu, Alpaslan Ozgun, Paul D Leger, Shilin Zhao, Fei Ye, Jason J Luke, Richard W Joseph, Rizwan Haq, Patrick A Ott, F Stephen Hodi, Jeffrey A Sosman, Douglas B Johnson, Elizabeth I Buchbinder
Anti-PD-1 therapy has improved clinical outcomes in advanced melanoma, but most patients experience intrinsic resistance. Responding patients can develop acquired resistance to anti-PD-1. We retrospectively reviewed 488 patients treated with anti-PD-1 from three academic centers and identified 36 patients with acquired resistance, defined as disease progression following objective response. The incidence, timing, disease sites, post-progression survival (PPS), and outcomes were evaluated descriptively. The acquired resistance cohort consisted of 67% with more than 1 feature of poor prognosis (stage M1c, elevated LDH, or brain metastasis), and 67% had previously received ipilimumab...
April 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28385737/lack-of-stat6-attenuates-inflammation-and-drives-protection-against-early-steps-of-colitis-associated-colon-cancer
#4
Sonia A Leon-Cabrera, Emmanuel Molina-Guzman, Yael G Delgado-Ramirez, Armando Vázquez-Sandoval, Yadira Ledesma-Soto, Carlos G Pérez-Plasencia, Yolanda I Chirino, Norma L Delgado-Buenrostro, Miriam Rodríguez-Sosa, Felipe Vaca-Paniagua, Federico Ávila-Moreno, Emma B Gutierrez-Cirlos, Luis E Arias-Romero, Luis I Terrazas
Colitis-associated colon cancer (CAC) is one of the most common malignant neoplasms and a leading cause of death. The immunologic factors associated with CAC development are not completely understood. Signal transducer and activator of transcription 6 (STAT6) is part of an important signaling pathway for modulating intestinal immune function and homeostasis. However, the role of STAT6 in colon cancer progression is unclear. Following CAC induction in wild-type (WT) and STAT6-deficient mice (STAT6(-/-)), we found that 70% of STAT6(-/-) mice were tumor-free after 8 weeks, whereas 100% of WT mice developed tumors...
April 6, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28351891/squamous-cell-tumors-recruit-%C3%AE-%C3%AE-t-cells-producing-either-il17-or-ifn%C3%AE-depending-on-the-tumor-stage
#5
Elena Lo Presti, Francesca Toia, Sebastiano Oieni, Simona Buccheri, Alice Turdo, Laura Rosa Mangiapane, Giuseppina Campisi, Valentina Caputo, Matilde Todaro, Giorgio Stassi, Adriana Cordova, Francesco Moschella, Gaetana Rinaldi, Serena Meraviglia, Francesco Dieli
The identification of reciprocal interactions between tumor-infiltrating immune cells and the microenviroment may help us understand mechanisms of tumor growth inhibition or progression. We have assessed the frequencies of tumor-infiltrating and circulating γδ T cells and regulatory T cells (Treg) from 47 patients with squamous cell carcinoma (SCC), to determine if they correlated with progression or survival. Vδ1 T cells infiltrated SSC tissue to a greater extent than normal skin, but SCC patients and healthy subjects had similar amounts circulating...
March 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28351890/targeting-cd47-and-autophagy-elicited-enhanced-antitumor-effects-in-non-small-cell-lung-cancer
#6
Xuyao Zhang, Jiajun Fan, Shaofei Wang, Yubin Li, Yichen Wang, Song Li, Jingyun Luan, Ziyu Wang, Ping Song, Qicheng Chen, Wenzhi Tian, Dianwen Ju
CD47-specific antibodies and fusion proteins that block CD47-SIRPα signaling are employed as antitumor agents for several cancers. Here, we investigated the synergistic antitumor effect of simultaneously targeting CD47 and autophagy in NSCLC. SIRPαD1-Fc, a novel CD47-targeting fusion protein, was generated and was found to increase the phagocytic and cytotoxic activities of macrophages against NSCLC cells. During this process, autophagy was markedly triggered, which was characterized by the three main stages of autophagic flux...
March 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28314751/identification-of-glycopeptides-as-post-translationally-modified-neoantigens-in-leukemia
#7
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/28254786/clinical-impact-of-tumor-dna-repair-expression-and-t-cell-infiltration-in-breast-cancers
#8
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/28159748/estradiol-promotes-breast-cancer-cell-migration-via-recruitment-and-activation-of-neutrophils
#9
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
#10
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
#11
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/28373217/diagnostic-comparison-of-ct-scans-and-colonoscopy-for-immune-related-colitis-in-ipilimumab-treated-advanced-melanoma-patients
#12
Marlene Garcia-Neuer, Melina E Marmarelis, Sushrut R Jangi, Jason J Luke, Nageatte Ibrahim, Meredith Davis, Janice Weinberg, Hilary Donahue, Nancy Bailey, F Stephen Hodi, Elizabeth L Buchbinder, Patrick A Ott
Colitis can be a life-threatening toxicity for patients treated with immune checkpoint blockade antibodies. With the anticipated widespread use of these reagents, the timely and accurate diagnosis of immune-related colitis becomes increasingly important. To better understand the clinical presentation of colitis from ipilimumab and to assess the use of CT scans of the abdomen/pelvis as a diagnostic tool, we retrospectively analyzed patients with advanced melanoma who received ipilimumab at our institution. Ninety nine (33%) of 303 patients developed diarrhea during therapy, and 46 patients (15%) received corticosteroids for colitis...
April 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28373216/report-on-the-fda-aacr-immuno-oncology-drug-development-workshop
#13
Colleen Curran, Elad Sharon
The FDA-AACR Immuno-oncology Drug Development Workshop was held in Washington, DC, from October 13 to 14, 2016. This interdisciplinary forum included government, industry, and academic leaders in pharmacology and oncology. The aim of the meeting was to discuss methodologies in nonclinical and clinical research, safety monitoring, efficacy endpoints, and statistical evaluation of cancer immunotherapy products. This summary highlights topics and viewpoints raised by the presenters and discussants and should not be viewed as the conclusions or recommendations of the workshop as a whole...
April 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28373215/masterful-antibodies-checkpoint-blockade
#14
REVIEW
Nils Lonberg, Alan J Korman
Cancer therapeutics that target the immune system rather than the cancer cell itself are becoming standard of care in a growing number of different malignancies. Although cancer immunotherapy is not a new concept, the potential importance of this class of drugs was probably not fully appreciated as recently as a decade ago when much of the focus of cancer drug discovery was on cancer cell-targeted medicines. The authors were lucky enough to be able to witness and participate in the discovery and development of ipilimumab and nivolumab, two relatively early examples of immune system-targeted drugs...
April 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28373214/about-the-masters
#15
REVIEW
(no author information available yet)
No abstract text is available yet for this article.
April 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28373213/george-klein-1925-2016-a-prescient-luminous-voice
#16
REVIEW
Pramod K Srivastava
No abstract text is available yet for this article.
April 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28373212/article-recommendations-from-our-deputy-and-senior-editors
#17
(no author information available yet)
No abstract text is available yet for this article.
April 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
#18
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 Kolhe, 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...
April 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28254787/serine-proteases-enhance-immunogenic-antigen-presentation-on-lung-cancer-cells
#19
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 V Heymach, Stephen G Swisher, Chantale Bernatchez, Gheath Alatrash, Samir 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 reinvigorated 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...
April 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
#20
Guillermo De Velasco, Youjin Je, Dominick Bossé, Mark M Awad, Patrick A Ott, Raphael B Moreira, Fabio Schutz, Joaquim Bellmunt, Guru P Sonpavde, F Stephen Hodi, Toni K Choueiri
Immune-related adverse events (irAE) have been described with immune checkpoint inhibitors (ICI), 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...
April 2017: Cancer Immunology Research
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