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Lung immunosuppression

Chiara Oltolini, Marco Ripa, Andrea Andolina, Elena Brioschi, Marta Cilla, Giovanna Petrella, Vanesa Gregorc, Barbara Castiglioni, Chiara Tassan Din, Paolo Scarpellini
The widespread use of T lymphocyte-associated antigen-4 (CTLA-4) and programmed death (PD)-1 and PD ligand-1 (PDL1)-targeted agents in cancer patients as immunotherapy has raised some issues on their safety profile. Regarding infectious complications, it has emerged that these compounds do not intrinsically increase susceptibility to opportunistic infections, which mainly correlate with the co-administration of systemic immunosuppressive therapy (high-dose corticosteroids and anti-tumor necrosis factors inhibitors) to cure immune-related adverse events (colitis, hepatitis, pneumonitis and pancreatitis), well-known complications of these targeted drugs...
August 13, 2018: Mycopathologia
Beatriz Wills, Julie R Brahmer, Jarushka Naidoo
Immune checkpoint inhibitors have revolutionized the management of advanced NSCLC. With the intention of generating an anti-tumor immune response, ICIs can also lead to inflammatory side effects involving a wide variety of organs in the body, termed immune-related adverse events. Although no prospective clinical trial exists to guide recommendations for optimal and more specific immunosuppressive treatments rather than corticosteroids, further studies may lead to a more mechanistic-based approach towards these toxicities in the future...
August 13, 2018: Current Treatment Options in Oncology
Naoto Oebisu, Manabu Hoshi, Makoto Ieguchi, Tadashi Iwai, Sayaka Tanaka, Masahiko Osawa, Hiroaki Nakamura
Methotrexate (MTX) is the key drug for the treatment of rheumatoid arthritis (RA). MTX-treated RA has been associated with the development of lymphoproliferative disorders (LPDs). Notably, the hyperimmune state of RA itself or the immunosuppressive state induced by MTX administration may contribute to development of LPD. Furthermore, Epstein-Barr virus (EBV) has been indicated to contribute to the development of MTX-LPD. MTX-associated LPD (MTX-LPD) may affect nodal or extranodal sites, including the gastrointestinal tract, skin, lungs, kidneys, and soft tissues, at an almost equal frequency...
August 2018: Molecular and Clinical Oncology
Jamie Sy Ho, Edwin R Chilvers, Muhunthan Thillai
Sarcoidosis is a multisystem granulomatous disease predominantly affecting the lungs, with increased risk of cardiovascular disease, pulmonary hypertension and cardiac sarcoidosis (CS), the latter due to direct granuloma infiltration. Sarcoidosis is often managed by chest physicians who need to understand the diagnostic pathways and initial management plans for patients with cardiac involvement. Areas covered: The most serious consequence of CS is sudden cardiac death due to ventricular tachyarrhythmias or complete atrioventricular block...
August 13, 2018: Expert Review of Respiratory Medicine
Ignacio Bender, Lilie L Lin, Lakshmi Rajdev, Elizabeth Chiao
This review highlights current interventional clinical trials for HIV-associated malignancies (HIVAMs), with emphasis on 4 mechanistic areas: immunomodulatory therapies and gene therapies, including immune checkpoint inhibitors; cytotoxic therapies; novel tumor-targeted and virally targeted therapies in both AIDS-defining and non-AIDS-defining cancers (NADC); and other screening or topical/ablative interventions. A search on located 35 trials, including 12 immunomodulatory or gene therapy trials, 6 cytotoxic therapy trials, 10 trials of therapies with tumor or viral molecular targets, and 7 trials evaluating screening interventions or topical or ablative therapies...
August 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Erin Reid, Gita Suneja, Richard F Ambinder, Kevin Ard, Robert Baiocchi, Stefan K Barta, Evie Carchman, Adam Cohen, Neel Gupta, Kimberly L Johung, Ann Klopp, Ann S LaCasce, Chi Lin, Oxana V Makarova-Rusher, Amitkumar Mehta, Manoj P Menon, David Morgan, Nitya Nathwani, Ariela Noy, Frank Palella, Lee Ratner, Stacey Rizza, Michelle A Rudek, Jeff Taylor, Benjamin Tomlinson, Chia-Ching J Wang, Mary A Dwyer, Deborah A Freedman-Cass
People living with HIV (PLWH) are diagnosed with cancer at an increased rate over the general population and generally have a higher mortality due to delayed diagnoses, advanced cancer stage, comorbidities, immunosuppression, and cancer treatment disparities. Lack of guidelines and provider education has led to substandard cancer care being offered to PLWH. To fill that gap, the NCCN Guidelines for Cancer in PLWH were developed; they provide treatment recommendations for PLWH who develop non-small cell lung cancer, anal cancer, Hodgkin lymphoma, and cervical cancer...
August 2018: Journal of the National Comprehensive Cancer Network: JNCCN
J Cuilleron, P Mas, L Kiakouama, L Gaillot-Durand, P Seve, G Devouassoux
Acquired hemophilia A (AHA) is a rare disease, defined by the production of anti-factor VIII antibodies causing disordered hemostasis. It is idiopathic in 50% of cases, but sometimes associated with solid tumors. We report a case where AHA led to the diagnosis of lung cancer. CASE REPORT: An 82-year-old man with spontaneous hematomas on his trunk and extremities, and isolated prolongation of activated partial thromboplastin time was admitted to the emergency room. A severely reduced factor VIII level and a high factor VIII inhibitor title confirmed the diagnosis of AHA...
August 8, 2018: Revue des Maladies Respiratoires
Katharina Maisel, Mervyn J Merrilees, Elena N Atochina-Vasserman, Lurong Lian, Kseniya Obraztsova, Ryan Rue, Alexander N Vasserman, Ning Zuo, Luis F Angel, Andrew J Gow, Inkyung Kang, Thomas N Wight, Evgeniy Eruslanov, Melody A Swartz, Vera P Krymskaya
Pulmonary Iymphangioleiomyomatosis (LAM) is a slow-progressing metastatic disease that is driven by mutations in the tumor suppressor tuberous sclerosis complex 1/2 (TSC1/2). Rapamycin inhibits LAM cell proliferation and is the only approved treatment, yet it can only stabilize the disease but not cause regression of existing lesions. However, in other cancers, immunotherapies such as checkpoint blockade against PD-1 and its ligand PD-L1 have shown promise in causing tumor regression and even curing some patients...
August 10, 2018: American Journal of Respiratory Cell and Molecular Biology
Ana Luísa Coelho, Mónica Patrícia Gomes, Raquel Jorge Catarino, Christian Rolfo, Rui Manuel Medeiros, António Manuel Araújo
Background: Lung cancer is the most incident and lethal form of cancer, with late diagnosis as a major determinant of its bad prognosis. Immunotherapies targeting immune checkpoints improve survival, but positive results encompass only 30%-40% of the patients, possibly due to alternative pathways to immunosuppression, including tumour-associated macrophages (TAM). Colony stimulating factor-1 (CSF-1) is implicated in TAM differentiation and recruitment to tumours and in tumour angiogenesis, through a special setting of Tie-2-expressing macrophages, which respond to angiopoietin-2 (Ang-2)...
2018: ESMO Open
Florentine Garaix, Marc Stern, François-Xavier Lamy, Laurence Dubel, Nassim Kamar
BACKGROUND Different pharmaceutical forms of oral tacrolimus allow tailored administration. The granular formulation facilitates accurate dose adjustment of tacrolimus according to patient characteristics, such as weight, or potential concomitant drug interactions. Currently, there are no data describing the use of tacrolimus granules in transplant recipients in France. MATERIAL AND METHODS OPTIMOD was a 6-month prospective, observational multicenter study that aimed to describe patient characteristics and conditions of use of tacrolimus granules...
August 10, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Dennis O Adeegbe, Shengwu Liu, Maureen Hattersley, Michaela Bowden, Chensheng W Zhou, Shuai Li, Raven Vlahos, Michael Grondine, Igor Dolgalev, Elena Ivanova, Max M Quinn, Peng Gao, Peter S Hammerman, James E Bradner, J Alan Diehl, Anil K Rustgi, Adam J Bass, Aristotelis Tsirigos, Gordon J Freeman, Huawei Chen, Kwok-Kin Wong
KRAS mutation is present in approximately 30% of human lung adenocarcinomas. Although recent advances in targeted therapy have shown great promise, effective targeting of KRAS remains elusive, and concurrent alterations in tumor suppressors render KRAS-mutant tumors even more resistant to existing therapies. Contributing to the refractoriness of KRAS-mutant tumors are immunosuppressive mechanisms, such as increased presence of suppressive regulatory T cells (Tregs) in tumors and elevated expression of the inhibitory receptor PD-1 on tumor-infiltrating T cells...
August 7, 2018: Cancer Immunology Research
Shuo Li, Zhe Wang, Xin-Ju Li
Evolution and progression of cancer always leads to CD8+ T cells dysfunction/exhaustion. Controversy remains as to the role of Notch signaling pathway in CD8+ T cells regulation in tumorigenesis. Thus, the aim of this study was to investigate the immunomodulatory activity of Notch signaling pathway to peripheral and lung-resident CD8+ T cells in patients with lung adenocarcinoma. Forty-eight lung adenocarcinoma patients and twenty healthy individuals were enrolled in the current study, and CD8+ T cells were purified from both peripheral bloods and bronchoalveolar lavage fluids...
August 4, 2018: International Immunopharmacology
Wenwen Zhang, Mengmeng Jiang, Jieying Chen, Rui Zhang, Yingnan Ye, Pengpeng Liu, Wenwen Yu, Jinpu Yu
Interleukin-6 (IL-6) is an important trigger for the expansion and recruitment of myeloid-derived suppressor cells (MDSCs), which are regarded to be major coordinators of the immunosuppressive tumor microenvironment. In this study, we constructed IL-6-knockdown breast cancer mice models to explore the molecular events involved in the IL-6-mediated effects on MDSC development. We defined a subset of early-stage MDSCs (e-MDSCs) with the phenotype of CD11b+ Gr-1- F4/80- MHCII- in IL-6 high-expressing 4T1 mice mammary carcinoma models, which were the precursors of CD11b+ Gr-1+ conventional MDSCs...
2018: Frontiers in Immunology
Andrea Botticelli, Bruna Cerbelli, Luana Lionetto, Ilaria Zizzari, Massimiliano Salati, Annalinda Pisano, Mazzuca Federica, Maurizio Simmaco, Marianna Nuti, Paolo Marchetti
BACKGROUND: Immune checkpoint inhibitors have revolutionized the treatment paradigm of highly lethal malignancies like advanced non-small cell lung cancer (NSCLC), demonstrating long-term tumour control and extended patient survival. Unfortunately, only 25-30% of patients experience a durable benefit, while the vast majority demonstrate primary or acquired resistance. Recently, indoleamine 2,3-dioxygenase (IDO) activity has been proposed as a possible mechanism of resistance to anti-PD-1 treatment leading to an immunosuppressive microenvironment...
August 6, 2018: Journal of Translational Medicine
Julie Alingrin, Benjamin Coiffard, Julien Textoris, Corine Nicolino-Brunet, Morgane Gossez, Pierre-André Jarrot, Françoise Dignat-George, Guillaume Monneret, Pascal Alexandre Thomas, Marc Leone, Martine Reynaud-Gaubert, Laurent Papazian
BACKGROUND: Immunosuppressive strategy targets mainly adaptive immunity after solid organ transplantation. We assessed the influence of early post-operative sepsis on T cell and monocyte reconstitution in anti-thymocyte globulin (ATG)-treated lung transplant recipients. METHODS: We retrospectively included recipients who underwent a first lung transplant at our Lung Transplant Center (Marseille, France) between July 2011 and February 2013. Peripheral blood T-lymphocyte subset counts and monocyte HLA-DR (mHLA-DR) expression routinely performed by flow cytometry within 60 days post-transplant were analyzed...
August 3, 2018: Transplant Immunology
Marlina Mansour, Lucas Hill, Janice Kerr
BACKGROUND: The direct acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection have sustained virologic response (SVR) rates of greater than 90% in most patients. However, data evaluating DAA use in transplant patients are limited. The goal of this study was to evaluate the effectiveness and safety of HCV treatment in this high-risk population. METHODOLOGY: This single-center retrospective study included liver, kidney, lung and/or heart transplant patients who were treated for HCV infection with DAAs...
August 6, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Valerio Leoni, Andrea Vannini, Valentina Gatta, Julie Rambaldi, Mara Sanapo, Catia Barboni, Anna Zaghini, Patrizia Nanni, Pier-Luigi Lollini, Costanza Casiraghi, Gabriella Campadelli-Fiume
Oncolytic herpes simplex viruses (oHSVs) showed efficacy in clinical trials and practice. Most of them gain cancer-specificity from deletions/mutations in genes that counteract the host response, and grow selectively in cancer cells defective in anti-viral response. Because of the deletions/mutations, they are frequently attenuated or over-attenuated. We developed next-generation oHSVs, which carry no deletion/mutation, gain cancer-specificity from specific retargeting to tumor cell receptors-e.g. HER2 (human epidermal growth factor receptor 2)-hence are fully-virulent in the targeted cancer cells...
August 6, 2018: PLoS Pathogens
Marta Lis-Sochocka, Patrycja Chylińska-Wrzos, Ewelina Wawryk-Gawda, Barbara Jodłowska-Jędrych
BACKGROUND: Cladribine is a useful immunosuppressive drug for the treatment of autoimmune diseases, leukemias and multiple sclerosis (MS). Despite the drug having low toxicity, side effects have been reported connected with myelosuppression, neutropenia and severe anemia. OBJECTIVES: The objective of this study was to investigate the influence of cladribine on lung pathomorphology and the expression of caspase 1 using immunohistochemistry method. MATERIAL AND METHODS: The study was conducted on Wistar rats, which were divided into: one control group (C) and one experimental group (E)...
August 6, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Mayumi Hatsuse, Yuka Daikoku, Yoko Taminishi, Shin-Ichi Fuchida, Yoshizumi Takemura, Akira Okano, Satoshi Murakami, Chihiro Shimazaki
A 73-year-old male who underwent splenectomy was diagnosed with splenic non-caseating granuloma in May 201X, and sarcoidosis was disregarded from the differential diagnosis. Owing to the persisting inflammation, the patient was carefully followed up with no treatment. Four months post splenectomy, the patient was hospitalized due to progressive dyspnea. Chest computed tomography revealed an encapsulated pleural effusion and lymphocytic infiltration in the left lower lung, with subclavian and mediastinal lymphadenopathy...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Claudie Laprise, Elizabeth K Cahoon, Charles F Lynch, Amy R Kahn, Glenn Copeland, Lou Gonsalves, Margaret M Madeleine, Ruth M Pfeiffer, Eric A Engels
Solid organ transplant recipients have an increased risk of lip cancer, but the reasons are uncertain. Using data from the Transplant Cancer Match Study, we describe the epidemiology of lip cancer among 261,500 transplant recipients in the United States. Two-hundred thirty-one lip cancers were identified, corresponding to elevated risks for both invasive and in situ lip cancers (standardized incidence ratios of 15.3 and 26.2, respectively). Invasive lip cancer incidence was associated with male sex (adjusted incidence rate ratio [aIRR] 2...
August 3, 2018: American Journal of Transplantation
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