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https://www.readbyqxmd.com/read/28806575/lessons-from-ctla-4-deficiency-and-checkpoint-inhibition
#1
REVIEW
Bernice Lo, Ussama M Abdel-Motal
CTLA-4 is a crucial negative regulator of immune responses. Absence of CTLA-4 in mice causes autoimmunity and lethal multiorgan lymphocytic infiltration and tissue destruction. Recently, heterozygous CTLA4 or biallelic LRBA mutations leading to functional CTLA-4 deficiency and autoimmunity have been discovered. LRBA was identified as a novel regulator of steady-state CTLA-4 protein levels in Tregs and activated T cells. CTLA-4 deficiency due to checkpoint blockade cancer immunotherapy has also been found to lead to autoimmune reactions...
August 11, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28805741/alcohol-and-cancer-mechanisms-and-therapies
#2
REVIEW
Anuradha Ratna, Pranoti Mandrekar
Several scientific and clinical studies have shown an association between chronic alcohol consumption and the occurrence of cancer in humans. The mechanism for alcohol-induced carcinogenesis has not been fully understood, although plausible events include genotoxic effects of acetaldehyde, cytochrome P450 2E1 (CYP2E1)-mediated generation of reactive oxygen species, aberrant metabolism of folate and retinoids, increased estrogen, and genetic polymorphisms. Here, we summarize the impact of alcohol drinking on the risk of cancer development and potential underlying molecular mechanisms...
August 14, 2017: Biomolecules
https://www.readbyqxmd.com/read/28805233/analytic-and-dynamic-secretory-profile-of-patient-derived-cytokine-induced-killer-cells
#3
Giulia Mesiano, Roberta Zini, Giulia Montagner, Nicoletta Bianchi, Rossella Manfredini, Antonella Chillemi, Massimo Aglietta, Giovanni Grignani, Ilaria Lampronti, Erika Fiorino, Fabio Malavasi, Dario Sangiolo, Roberto Gambari, Davide Ferrari
Adoptive immunotherapy with Cytokine Induced Killer (CIK) cells has shown antitumor activity against several kinds of cancers in preclinical models and clinical trials. CIK cells are a subset of ex vivo expanded T lymphocytes with T-NK phenotype and MHC-unrestricted antitumor activity. Literature provides scanty information on cytokines, chemokines and growth factors secreted by CIK cells. Therefore, we investigated the secretory profile of CIK cells generated from tumor patients. The secretome analysis was performed at specific time points (day 1, day 14 and day 21) of CIK cells expansion...
August 9, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28804691/combination-of-celecoxib-celebrex-%C3%A2-and-cd19-car-redirected-ctl-immunotherapy-for-the-treatment-of-b-cell-non-hodgkin-s-lymphomas
#4
REVIEW
Tam Nm Dinh, Alexandra S Onea, Ali R Jazirehi
The nonsteroidal anti-inflammatory drug (NSAID) Celecoxib (Celebrex(®)) received Food and Drug Administration (FDA) approval in 1998 for treatment of osteoarthritis and rheumatoid arthritis, and in recent years, its use has been extended to various types of malignancies, such as breast, colon, and urinary cancers. To maintain the survival of malignant B cells, non-Hodgkin's Lymphoma (NHL) is highly dependent on inflammatory microenvironment, and is inhibited by celecoxib. Celecoxib hinders tumor growth interacting with various apoptotic genes, such as cyclooxygenase-2 (Cox-2), B-cell lymphoma 2 (Bcl-2) family, phosphor-inositide-3 kinase/serine-threonine-specific protein kinase (PI3K/Akt), and inhibitors of apoptosis proteins (IAP) family...
2017: American Journal of Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28804489/normalized-synergy-predicts-that-cd8-co-receptor-contribution-to-t-cell-receptor-tcr-and-pmhc-binding-decreases-as-tcr-affinity-increases-in-human-viral-specific-t-cells
#5
Chad M Williams, Alexandra A Schonnesen, Shu-Qi Zhang, Ke-Yue Ma, Chenfeng He, Tori Yamamoto, S Gail Eckhardt, Christopher A Klebanoff, Ning Jiang
The discovery of naturally occurring T cell receptors (TCRs) that confer specific, high-affinity recognition of pathogen and cancer-associated antigens remains a major goal in cellular immunotherapies. The contribution of the CD8 co-receptor to the interaction between the TCR and peptide-bound major histocompatibility complex (pMHC) has previously been correlated with the activation and responsiveness of CD8(+) T cells. However, these studies have been limited to model systems of genetically engineered hybridoma TCRs or transgenic mouse TCRs against either a single epitope or an array of altered peptide ligands...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28803798/radiosynthesis-and-preclinical-pet-evaluation-of-89-zr-nivolumab-bms-936558-in-healthy-non-human-primates
#6
Erin L Cole, Joonyoung Kim, David J Donnelly, R Adam Smith, Daniel Cohen, Virginie Lafont, Paul E Morin, Richard Y-C Huang, Patrick L Chow, Wendy Hayes, Samuel Bonacorsi
Cancer immunotherapy, unlike traditional cytotoxic chemotherapeutic treatments, engages the immune system to identify cancer cells and stimulate immune responses. The Programmed Death-1 (PD-1) protein is an immunoinhibitory receptor expressed by activated cytotoxic T-lymphocytes (CTL) that seek out and destroy cancer cells. Multiple cancer types express and upregulate the Programmed Death-Ligand 1 (PD-L1) and 2 (PD-L2) which bind to PD-1 as an immune escape mechanism. Nivolumab is a fully human IgG4 anti-PD-1 monoclonal antibody (mAb) approved for treatment of multiple cancer types...
August 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28803721/conditioning-neoadjuvant-therapies-for-improved-immunotherapy-of-cancer
#7
REVIEW
Zachary Benson, Saeed H Manjili, Mehran Habibi, Georgi Guruli, Amir A Toor, Kyle K Payne, Masoud H Manjili
Recent advances in the treatment of melanoma and non-small cell lung cancer (NSCLC) by combining conventional therapies with anti-PD1/PD-L1 immunotherapies, have renewed interests in immunotherapy of cancer. The emerging concept of conventional cancer therapies combined with immunotherapy differs from the classical concept in that it is not simply taking advantage of their additive anti-tumor effects, but it is to use certain therapeutic regimens to condition the tumor microenvironment for optimal response to immunotherapy...
August 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28803259/opportunities-and-challenges-in-the-immunological-therapy-of-pediatric-malignancy-a-concise-snapshot
#8
REVIEW
Francesco Ceppi, Maja Beck-Popovic, Jean-Pierre Bourquin, Raffaele Renella
Over the last 50 years, collaborative clinical trials have reduced the number of children dying from pediatric cancer significantly. Unfortunately, certain tumor types have remained resistant to conventional surgical, radiotherapy and chemotherapy combinations, and relapsing and/or refractory disease remains associated with dismal outcomes. Recently, renewed attention has been given to the role for immunotherapies in pediatric oncology. In fact, these combine several attractive features, including (but possibly not limited to) the specificity for cancer cells, potentially in vivo persistence and longevity, and potency against refractory disease...
August 12, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/28802832/retroviral-gene-transfer-into-primary-human-nk-cells-activated-by-il-2-and-k562-feeder-cells-expressing-membrane-bound-il-21
#9
Maria A Streltsova, Eugene Barsov, Sofia A Erokhina, Elena I Kovalenko
Natural killer (NK) cells are capable of rapidly recognizing and efficiently killing tumor cells. This makes them a potentially promising agent for cancer immunotherapy. Additional genetic modifications of NK cells may further improve their anti-tumor efficacy. Numerous technical challenges associated with gene delivery into NK cells have significantly tempered this approach. We achieved efficient retroviral vector transduction of primary human NK cells that were stimulated by a combination of IL-2 and engineered K562 cells expressing membrane-bound IL-21...
August 9, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28801472/breast-cancer-immunotherapy-facts-and-hopes
#10
Leisha A Emens
Immunotherapy is revolutionizing the management of multiple solid tumors, and early data have revealed the clinical activity of PD-1/PD-L1 antagonists in small numbers of metastatic breast cancer patients. Clinical activity appears more likely if the tumor is triple negative, PD-L1+, and/or harbors higher levels of TILs. Responses to atezolizumab and pembrolizumab appear to be durable in metastatic triple negative breast cancer (TNBC), suggesting these agents may transform the lives of responding patients. Current clinical efforts are focused on developing immunotherapy combinations that convert non-responders to responders, deepen those responses that do occur, and surmount acquired resistance to immunotherapy...
August 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28801444/radical-cystectomy-bladder-removal-against-intravesical-bcg-immunotherapy-for-high-risk-non-muscle-invasive-bladder-cancer-bravo-a-protocol-for-a-randomised-controlled-feasibility-study
#11
Jamie B Oughton, Heather Poad, Maureen Twiddy, Michelle Collinson, Victoria Hiley, Kathryn Gordon, Mark Johnson, Sunjay Jain, Aidan P Noon, Rohit Chahal, Matt Simms, Mohantha Dooldeniya, Phillip Koenig, Louise Goodwin, Julia M Brown, James W F Catto
INTRODUCTION: High-risk non-muscle invasive bladder cancer (HRNMIBC) is a heterogeneous disease that can be difficult to predict. While around 25% of cancers progress to invasion and metastases, the remaining majority of tumours remain within the bladder. It is uncertain whether patients with HRNMIBC are better treated with intravesical maintenance BCG (mBCG) immunotherapy or primary radical cystectomy (RC). A definitive randomised controlled trial (RCT) is needed to compare these two different treatments but may be difficult to recruit to and has not been attempted to date...
August 11, 2017: BMJ Open
https://www.readbyqxmd.com/read/28801287/-th1-th2-and-treg-th17-cell-balance-in-peripheral-blood-of-patients-with-ovarian-cancer
#12
Li-Hua Wang, Liang-Liang Wang, Jing Zhang, Pei Zhang, Sheng-Ze Li
OBJECTIVE: To investigate the changes in the percentages and balance of CD4(+)T cell subsets including T helper cells (Thl, Th2, and Thl7) and T regulatory cells (Treg) in patients with ovarian cancer. METHODS: Peripheral blood samples were collected from 30 patients with ovarian cancer and 20 healthy subjects for analysis of the percentages of Thl, Th2, Thl7 and Treg using flow cytometry. RESULTS: Compared with the control subjects, the patients with ovarian cancer showed significantly increased percentages of Th2, Thl7 and Treg (P<0...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28801026/quadruple-immunotherapy-of-bacillus-calmette-gu%C3%A3-rin-interferon-interleukin-2-and-granulocyte-macrophage-colony-stimulating-factor-as-salvage-therapy-for-non-muscle-invasive-bladder-cancer
#13
Ryan L Steinberg, Kenneth G Nepple, Kyla N Velaer, Lewis J Thomas, Michael A O'Donnell
BACKGROUND: Bacillus Calmette-Guérin (BCG) is the most effective initial intravesical therapy for high-grade non-muscle invasive bladder cancer, but many patients still fail. Combination intravesical BCG and interferon (IFN) will salvage some patients but results remain suboptimal. OBJECTIVE: We hypothesized that further immunostimulation with intravesical interleukin-2 and subcutaneous granulocyte-macrophage colony-stimulating factor may improve response to intravesical BCG and IFN in patient with prior BCG failure(s)...
August 8, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28800469/immunotherapy-in-ovarian-endometrial-and-cervical-cancer-state-of-the-art-and-future-perspectives
#14
REVIEW
Jole Ventriglia, Immacolata Paciolla, Carmela Pisano, Sabrina Chiara Cecere, Marilena Di Napoli, Rosa Tambaro, Daniela Califano, Simona Losito, Giosuè Scognamiglio, Sergio Venanzio Setola, Laura Arenare, Sandro Pignata, Chiara Della Pepa
The tumors of the female genital tract represent a leading cause of morbidity and mortality among women worldwide. Substantial progresses have been made in ovarian cancer, with the increasing knowledge about BRCA mutated tumors and the recent development of PARP inhibitors, and in cervical cancer, thanks to extensive screening and widespread of vaccination against Human Papilloma Virus. Nevertheless many needs remain unmet, advanced stage diseases are still incurable and cervical and endometrial carcinoma, as well as platinum-resistant ovarian carcinoma, can certainly be classifiable among the cancers with poor sensitivity to conventional chemotherapy...
July 31, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28799818/the-expression-and-clinical-signification-of-pd-1-in-lymph-nodes-of-patients-with-non-small-cell-lung-cancer
#15
Haitao Ma, GuoCai Mao, GuangBo Zhang, HaiTao Huang
To screen anti-programmed cell death protein 1 (PD-1) antibody treatment of the dominant population, it is necessary to understand the expression of PD-1 in tumor metastasis microenvironment. The aim of the present study was to detect the expression of PD-1 in lymph nodes of 51 patients with non-small cell lung cancer (NSCLC) by using flow cytometry (FCM). The results showed that the PD-1 expression on CD3(+) T cells was significantly increased in NSCLC metastatic lymph nodes (50.08 ± 8.03%) compared with nonmetastatic lymph nodes (36...
August 11, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28799073/immunotherapy-in-breast-cancer-the-emerging-role-of-pd-1-and-pd-l1
#16
REVIEW
François Bertucci, Anthony Gonçalves
PURPOSE OF REVIEW: The purpose of the review is to summarize the data regarding PD-L1 expression in breast cancer and the results of first clinical trials with PD-1 or PD-L1 inhibitors in patients with metastatic breast cancer. RECENT FINDINGS: PD-L1 expression is heterogeneous across primary breast cancers, and is generally associated with the presence of tumor-infiltrating lymphocytes and the presence of poor-prognosis features such as high grade, and aggressive molecular subtypes (triple-negative (TN), basal, HER2-enriched)...
August 10, 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28798332/absence-of-grail-promotes-cd8-t-cell-anti-tumour-activity
#17
Cara Haymaker, Yi Yang, Junmei Wang, Qiang Zou, Anupama Sahoo, Andrei Alekseev, Divyendu Singh, Krit Ritthipichai, Yared Hailemichael, Oanh N Hoang, Hong Qin, Kimberly S Schluns, Tiejun Wang, Willem W Overwijk, Shao-Cong Sun, Chantale Bernatchez, Larry W Kwak, Sattva S Neelapu, Roza Nurieva
T-cell tolerance is a major obstacle to successful cancer immunotherapy; thus, developing strategies to break immune tolerance is a high priority. Here we show that expression of the E3 ubiquitin ligase Grail is upregulated in CD8(+) T cells that have infiltrated into transplanted lymphoma tumours, and Grail deficiency confers long-term tumour control. Importantly, therapeutic transfer of Grail-deficient CD8(+) T cells is sufficient to repress established tumours. Mechanistically, loss of Grail enhances anti-tumour reactivity and functionality of CD8(+) T cells...
August 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28798308/prognostic-value-of-programmed-cell-death-protein-1-expression-on-cd8-t-lymphocytes-in-pancreatic-cancer
#18
Tao Shen, Liangjing Zhou, Hua Shen, Chengfei Shi, Shengnan Jia, Guo Ping Ding, Liping Cao
Pancreatic cancer is one of the most aggressive malignancies and has a highly immunosuppressive tumour microenvironment. Immune checkpoint blockade has led to remarkable and durable objective responses in a number of malignancies and antibody-based strategies targeting programmed cell death protein 1 (PD-1) are showing promise where traditional modalities of surgery, radiotherapy, and chemotherapy have failed. In this study, we examined the clinical value of PD-1 protein expression by CD8+ peripheral T lymphocytes or tumour-infiltrating T lymphocytes (TILs) in pancreatic ductal adenocarcinoma (PDAC)...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28798090/egfr-tyrosine-kinase-inhibitors-versus-chemotherapy-in-egfr-wild-type-pre-treated-advanced-nonsmall-cell-lung-cancer-in%C3%A2-daily-practice
#19
Pascale Tomasini, Solenn Brosseau, Julien Mazières, Jean-Philippe Merlio, Michèle Beau-Faller, Jean Mosser, Marie Wislez, L'Houcine Ouafik, Benjamin Besse, Isabelle Rouquette, Didier Debieuvre, Fabienne Escande, Virginie Westeel, Clarisse Audigier-Valette, Pascale Missy, Alexandra Langlais, Frank Morin, Denis Moro-Sibilot, Gérard Zalcman, Fabrice Barlesi
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are approved for second-line treatment of EGFR wild-type (EGFR-wt) nonsmall cell lung cancer (NSCLC). However, results from randomised trials performed to compare EGFR-TKIs with chemotherapy in this population did not show any survival benefit. In the era of immunotherapy, many drugs are approved for second-line treatment of EGFR-wt NSCLC and there is a need to reassess the role of EGFR-TKIs in this setting.The Biomarkers France study is a large nationwide cohort of NSCLC patients tested for EGFR mutations...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28798088/immune-checkpoint-inhibitors-associated-with-interstitial-lung-disease-in-cancer-patients
#20
Myriam Delaunay, Jacques Cadranel, Amélie Lusque, Nicolas Meyer, Valérie Gounaut, Denis Moro-Sibilot, Jean-Marie Michot, Judith Raimbourg, Nicolas Girard, Florian Guisier, David Planchard, Anne-Cécile Metivier, Pascale Tomasini, Eric Dansin, Maurice Pérol, Marion Campana, Oliver Gautschi, Martin Früh, Jean-David Fumet, Clarisse Audigier-Valette, Sébastien Couraud, Stéphane Dalle, Marie-Thérèse Leccia, Marion Jaffro, Samia Collot, Grégoire Prévot, Julie Milia, Julien Mazieres
Immunotherapy is becoming a standard of care for many cancers. Immune-checkpoint inhibitors (ICI) can generate immune-related adverse events. Interstitial lung disease (ILD) has been identified as a rare but potentially severe event.Between December 2015 and April 2016, we conducted a retrospective study in centres experienced in ICI use. We report the main features of ICI-ILD with a focus on clinical presentation, radiological patterns and therapeutic strategies.We identified 64 (3.5%) out of 1826 cancer patients with ICI-ILD...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
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