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Lung cancer, immunotherapy

Jason Roszik, Lauren E Haydu, Kenneth R Hess, Junna Oba, Aron Y Joon, Alan E Siroy, Tatiana V Karpinets, Francesco C Stingo, Veera Baladandayuthapani, Michael T Tetzlaff, Jennifer A Wargo, Ken Chen, Marie-Andrée Forget, Cara L Haymaker, Jie Qing Chen, Funda Meric-Bernstam, Agda K Eterovic, Kenna R Shaw, Gordon B Mills, Jeffrey E Gershenwald, Laszlo G Radvanyi, Patrick Hwu, P Andrew Futreal, Don L Gibbons, Alexander J Lazar, Chantale Bernatchez, Michael A Davies, Scott E Woodman
BACKGROUND: While clinical outcomes following immunotherapy have shown an association with tumor mutation load using whole exome sequencing (WES), its clinical applicability is currently limited by cost and bioinformatics requirements. METHODS: We developed a method to accurately derive the predicted total mutation load (PTML) within individual tumors from a small set of genes that can be used in clinical next generation sequencing (NGS) panels. PTML was derived from the actual total mutation load (ATML) of 575 distinct melanoma and lung cancer samples and validated using independent melanoma (n = 312) and lung cancer (n = 217) cohorts...
October 25, 2016: BMC Medicine
J Chee, B W S R Robinson, R A Holt, J Creaney
Harnessing the immune system to fight cancer is an exciting advancement in lung cancer therapy. Anti-tumor immunity can be augmented by checkpoint blockade therapy, which removes the inhibition/brakes imposed on the immune system by the tumor. Checkpoint blockade therapy with anti-PD1/anti-PDL1 antibodies causes tumor regression in around 25% of lung cancer patients. In another approach, the immune system is forced or accelerated to attack the tumour, via augmentation of the anti-tumour response against mutations carried by each lung tumour...
October 18, 2016: Chest
Ettore D'Argento, Sabrina Rossi, Giovanni Schinzari, Antonia Strippoli, Michele Basso, Alessandra Cassano, Carlo Barone
New treatments-as immunotherapies and new antiangiogenic agents-are now available in second-line setting for patients affected by EGFR wild-type and ALK-negative non-small-cell lung cancer (NSCLC). Nintedanib, ramucirumab, nivolumab and pembrolizumab have to be included in the therapeutic sequences for patients affected by NSCLC, but no clear selection criteria are to date offered, except for patients with PD-L1 expression ≥50 %. Performance status, smoking habits and comorbidities should be considered as clinical criteria in order to select the appropriate treatment, but also tumour characteristics as histotype, platinum resistance and rapid progression after a first-line therapy should be taken into account...
December 2016: Current Treatment Options in Oncology
Yoichi Kato
We assessed the efficacy of WT1 class I peptide and WT1 class II peptide pulsed dendritic cell(DC)therapy for a wide range of advanced cancers. This retrospective study included 60 advanced cancer patients who were vaccinated 5times or more in this clinic between September 2013 and December 2015. The clinical response was examined. This treatment was approved by the ethics panel at this institution. Sixty patients were injected an average of 6.15times with dendritic cells(DCs) (2.6×10 / 7 cells/injection)...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Shouzheng Wang, Junling Li
In recent years, squamous non-small cell lung cancer (NSCLC) didn't progress much in chemotherapy or target therapy. However, immunotherapy has made breakthroughs in treating squamous NSCLC. Immunotherapy includes two main broad classes of immune checkpoint inhibitors and therapeutic vaccines. Immune checkpoint inhibitors, including anti cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and anti programmed death receptor 1 (PD-1) antibodies, have been tested in the phase II/III clinical trials and have demonstrated promising outcomes...
October 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Frederick J Kohlhapp, Erica J Huelsmann, Andrew T Lacek, Jason M Schenkel, Jevgenijs Lusciks, Joseph R Broucek, Josef W Goldufsky, Tasha Hughes, Janet P Zayas, Hubert Dolubizno, Ryan T Sowell, Regina Kühner, Sarah Burd, John C Kubasiak, Arman Nabatiyan, Sh'Rae Marshall, Praveen K Bommareddy, Shengguo Li, Jenna H Newman, Claude E Monken, Sasha H Shafikhani, Amanda L Marzo, Jose A Guevara-Patino, Ahmed Lasfar, Paul G Thomas, Edmund C Lattime, Howard L Kaufman, Andrew Zloza
In light of increased cancer prevalence and cancer-specific deaths in patients with infections, we investigated whether infections alter anti-tumor immune responses. We report that acute influenza infection of the lung promotes distal melanoma growth in the dermis and leads to accelerated cancer-specific host death. Furthermore, we show that during influenza infection, anti-melanoma CD8(+) T cells are shunted from the tumor to the infection site, where they express high levels of the inhibitory receptor programmed cell death protein 1 (PD-1)...
October 18, 2016: Cell Reports
Behjatolah Monzavi-Karbassi, Fariba Jousheghany, Thomas Kieber-Emmons
Development of cancer vaccines targeting tumor-associated antigens (TAAs) is an alternative approach to chemotherapy with sustained anti-tumor effects. The success of active immunotherapy has been hampered by tumor-induced immune suppressors. Regulatory T cells (Tregs) are a population of immune suppressors with a proven role in regulating anti-tumor immune responses. Removing or subduing Tregs activity leads to more robust anti-tumor immune responses. Here, we used a cell-based vaccination strategy in the 4T1 murine mammary model to examine whether bulk removal of certain TAAs, using their glycan profile, can affect the immunogenicity of the vaccine...
October 19, 2016: Immunological Investigations
David J Pinato, Robert J Shiner, Solomon D T White, James R M Black, Pritesh Trivedi, Justin Stebbing, Rohini Sharma, Francesco A Mauri
Purpose: There is inconclusive evidence to suggest the expression of programmed cell death (PD) ligand 1 (PD-L1) is a putative predictor of response to PD-1/PD-L1-targeted therapies in lung cancer. We evaluated the heterogeneity in the expression of PD-1 ligands in isogeneic primary and metastatic LC specimens. Experimental Design: From 12,580 post mortem cases, we identified 214 patients with untreated metastatic LC, of which 98 had adequately preserved tissues to construct a syngeneic primary LC/metastasis tissue microarray...
2016: Oncoimmunology
Denghai Mi, Weiwei Ren, Kehu Yang
BACKGROUND & OBJECTIVES: The effectiveness of interleukin-2 (IL-2) and induced killer cells for non-small cell lung cancer (NSCLC) is controversial. This study evaluates the efficacy and safety of interleukin-2 and induced killer cells on NSCLC, so as to provide references for further clinical practice and research. METHODS: Relevant randomized controlled trials (RCTs) were searched in Cochrane library (Issue 2, 2013), Web of Science (1980-March 2013), PubMed (1966-March 2013), China Knowledge Resource Integrated database (CNKI) (1994-March 2013), China Biology Medicine database (CBM) (1978-March 2013), VIP (1989-March 2013), and Wan Fang databases (1997-March 2013)...
May 2016: Indian Journal of Medical Research
Juergen Kast
No abstract text is available yet for this article.
September 2016: Journal of Thoracic Disease
Kristen A Marrone, Jarushka Naidoo, Julie R Brahmer
The treatment paradigm for lung cancer has been transformed in recent years by the use of immunotherapy, specifically, immune checkpoint antibodies (mAb), which are agents designed to reinvigorate an immune-mediated anticancer response by releasing the effects of tumor-mediated immunosuppression. Late-phase clinical trials of these agents in patients with advanced lung cancers have translated into improved clinical outcomes compared with standard-of-care chemotherapy for the treatment of metastatic non-small cell lung cancer, and have resulted in FDA approvals for two immune checkpoint mAbs in the second-line setting...
October 2016: Seminars in Respiratory and Critical Care Medicine
Christian Manegold, Anne-Marie C Dingemans, Jhanelle E Gray, Kazuhiko Nakagawa, Marianne Nicolson, Solange Peters, Martin Reck, Yi-Long Wu, Odd Terje Brustugun, Lucio Crino, Enriqueta Felip, Dean Fennell, Pilar Garrido, Rudolf M Huber, Aurelien Marabelle, Marcin Moniuszko, Francoise Mornex, Silvia Novello, Mauro Papotti, Maurice Pérol, Egbert F Smit, Kostas Syrigos, Jan P van Meerbeeck, Nico van Zandwijk, James Chih-Hsin Yang, Caicun Zhou, Everett Vokes
Over the past few years, there have been considerable advances in the treatments available to patients with metastatic or locally advanced non-small cell lung cancer (NSCLC), particularly those who have progressed on or during first-line treatment. Some of the treatment options available to patients are discussed here, with a focus on checkpoint inhibitor immunotherapies (nivolumab and pembrolizumab) and antiangiogenic agents (bevacizumab, ramucirumab and nintedanib). It is hypothesised that combining immunotherapy with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments...
October 8, 2016: Journal of Thoracic Oncology
Romain Daillère, Marie Vétizou, Nadine Waldschmitt, Takahiro Yamazaki, Christophe Isnard, Vichnou Poirier-Colame, Connie P M Duong, Caroline Flament, Patricia Lepage, Maria Paula Roberti, Bertrand Routy, Nicolas Jacquelot, Lionel Apetoh, Sonia Becharef, Sylvie Rusakiewicz, Philippe Langella, Harry Sokol, Guido Kroemer, David Enot, Antoine Roux, Alexander Eggermont, Eric Tartour, Ludger Johannes, Paul-Louis Woerther, Elisabeth Chachaty, Jean-Charles Soria, Encouse Golden, Silvia Formenti, Magdalena Plebanski, Mutsa Madondo, Philip Rosenstiel, Didier Raoult, Vincent Cattoir, Ivo Gomperts Boneca, Mathias Chamaillard, Laurence Zitvogel
The efficacy of the anti-cancer immunomodulatory agent cyclophosphamide (CTX) relies on intestinal bacteria. How and which relevant bacterial species are involved in tumor immunosurveillance, and their mechanism of action are unclear. Here, we identified two bacterial species, Enterococcus hirae and Barnesiella intestinihominis that are involved during CTX therapy. Whereas E. hirae translocated from the small intestine to secondary lymphoid organs and increased the intratumoral CD8/Treg ratio, B. intestinihominis accumulated in the colon and promoted the infiltration of IFN-γ-producing γδT cells in cancer lesions...
September 28, 2016: Immunity
Kirollos S Hanna
PURPOSE: Pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, is a humanized monoclonal antibody used in the treatment of metastatic or unresectable melanoma and advanced non-small cell lung cancer (NSCLC). We hereby report a case of pembrolizumab-induced uveitis to increase practitioner awareness. CASE REPORT: A 78-year-old female presented with onset of panuveitis after initiation of pembrolizumab therapy for metastatic melanoma. The patient received three cycles of therapy every 21 days during which her symptoms progressively worsened...
September 26, 2016: Pharmacotherapy
Pankit Vachhani, Hongbin Chen
Immunotherapy with immune checkpoint inhibitors has opened a new arena in cancer therapeutics. Pembrolizumab is a highly selective anti-programmed cell death protein 1 (PD-1) antibody that has shown efficacy, leading to survival benefit and durable responses, in some patients with non-small cell lung cancer (NSCLC). It has been approved by the US Food and Drug Administration for the treatment of patients with metastatic NSCLC, whose tumors express PD-1 ligand 1 (PD-L1), with disease progression on or after platinum-containing chemotherapy...
2016: OncoTargets and Therapy
Anne Mobergslien, Qian Peng, Vlada Vasovic, Mouldy Sioud
Therapeutic strategies aiming at mobilizing immune effector cells to kill tumor cells independent of tumor mutational load and MHC expression status are expected to benefit cancer patients. Recently, we engineered various peptide-Fc fusion proteins for directing Fcg receptor-bearing immune cells toward tumor cells. Here, we investigated the immunostimulatory and anti-tumor effects of one of the engineered Fc fusion proteins (WN-Fc). In contrast to the Fc control, soluble WN-Fc-1 fusion protein activated innate immune cells (e...
October 4, 2016: Oncotarget
Leila Khoja, Minnie Kibiro, Ur Metser, Craig Gedye, David Hogg, Marcus O Butler, Eshetu G Atenafu, Anthony M Joshua
BACKGROUND: Radiological assessment of response to checkpoint inhibitors remains imperfect. We evaluated individual lesion and inter-patient response by response evaluation (RECIST) 1.1, immune-related response criteria (irRC), CHOI and modified CHOI (mCHOI) and correlated response with overall survival (OS). METHODS: Thirty-seven patients with 567 measurable lesions treated with pembrolizumab in the Keynote 001 trial were studied. Association of response with OS was determined...
October 4, 2016: British Journal of Cancer
Grit S Herter-Sprie, Shohei Koyama, Houari Korideck, Josephine Hai, Jiehui Deng, Yvonne Y Li, Kevin A Buczkowski, Aaron K Grant, Soumya Ullas, Kevin Rhee, Jillian D Cavanaugh, Neermala Poudel Neupane, Camilla L Christensen, Jan M Herter, G Mike Makrigiorgos, F Stephen Hodi, Gordon J Freeman, Glenn Dranoff, Peter S Hammerman, Alec C Kimmelman, Kwok-Kin Wong
Radiation therapy (RT), a critical modality in the treatment of lung cancer, induces direct tumor cell death and augments tumor-specific immunity. However, despite initial tumor control, most patients suffer from locoregional relapse and/or metastatic disease following RT. The use of immunotherapy in non-small-cell lung cancer (NSCLC) could potentially change this outcome by enhancing the effects of RT. Here, we report significant (up to 70% volume reduction of the target lesion) and durable (up to 12 weeks) tumor regressions in conditional Kras-driven genetically engineered mouse models (GEMMs) of NSCLC treated with radiotherapy and a programmed cell death 1 antibody (αPD-1)...
June 16, 2016: JCI Insight
Patrick H Lizotte, Elena V Ivanova, Mark M Awad, Robert E Jones, Lauren Keogh, Hongye Liu, Ruben Dries, Christina Almonte, Grit S Herter-Sprie, Abigail Santos, Nora B Feeney, Cloud P Paweletz, Meghana M Kulkarni, Adam J Bass, Anil K Rustgi, Guo-Cheng Yuan, Donald W Kufe, Pasi A Jänne, Peter S Hammerman, Lynette M Sholl, F Stephen Hodi, William G Richards, Raphael Bueno, Jessie M English, Mark A Bittinger, Kwok-Kin Wong
BACKGROUND. Immune checkpoint blockade improves survival in a subset of patients with non-small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. METHODS. We performed comprehensive flow cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next-generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC)...
September 8, 2016: JCI Insight
Dijana Djureinovic, Björn M Hallström, Masafumi Horie, Johanna Sofia Margareta Mattsson, Linnea La Fleur, Linn Fagerberg, Hans Brunnström, Cecilia Lindskog, Katrin Madjar, Jörg Rahnenführer, Simon Ekman, Elisabeth Ståhle, Hirsh Koyi, Eva Brandén, Karolina Edlund, Jan G Hengstler, Mats Lambe, Akira Saito, Johan Botling, Fredrik Pontén, Mathias Uhlén, Patrick Micke
Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs...
July 7, 2016: JCI Insight
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