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https://www.readbyqxmd.com/read/29902298/prevalence-of-pdl1-amplification-and-preliminary-response-to-immune-checkpoint-blockade-in-solid-tumors
#1
Aaron M Goodman, David Piccioni, Shumei Kato, Amélie Boichard, Huan-You Wang, Garrett Frampton, Scott M Lippman, Caitlin Connelly, David Fabrizio, Vincent Miller, Jason K Sicklick, Razelle Kurzrock
Importance: Copy number alterations in programmed cell death ligand 1 (PDL1 or CD274), programmed cell death 1 ligand 2 (PDCD1LG2 or PDL2), and Janus kinase 2 (JAK2) genes (chromosome 9p24.1) characterize Hodgkin lymphoma, resulting in high response rates to programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) blockade. The prevalence and utility of PDL1 amplification as a response biomarker to PD-1/PD-L1 blockade are unknown in other tumors. Objectives: To examine the prevalence of PDL1 amplification and its utility as a response biomarker to PD-1/PD-L1 blockade in solid tumors...
June 14, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29898687/pd-l1-assessment-in-pediatric-rhabdomyosarcoma-a-pilot-study
#2
Giulia Bertolini, Luca Bergamaschi, Andrea Ferrari, Salvatore L Renne, Paola Collini, Cecilia Gardelli, Marta Barisella, Giovanni Centonze, Stefano Chiaravalli, Cinzia Paolino, Massimo Milione, Maura Massimino, Michela Casanova, Patrizia Gasparini
BACKGROUND: Rhabdomyosarcomas (RMSs) are the most frequent soft tissue sarcoma in children and adolescents, defined by skeletal muscle differentiation and the status of FOXO1 fusions. In pediatric malignancies, in particular RMS, scant and controversial observations are reported about PD-L1 expression as a putative biomarker and few immune checkpoint clinical trials are conducted. METHODS: PD-L1 assessment was evaluated by immunohistochemistry (IHC) utilizing two anti-PDL1 antibodies, in a pilot cohort of 25 RMS...
June 13, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29888503/elevation-of-the-tp53-isoform-%C3%AE-133p53%C3%AE-in-glioblastomas-an-alternative-to-mutant-p53-in-promoting-tumour-development
#3
Marina Kazantseva, Ramona A Eiholzer, Sunali Mehta, Ahmad Taha, Sara Bowie, Imogen Roth, Jean Zhou, Sebastien M Joruiz, Janice A Royds, Noelyn A Hung, Tania L Slatter, Antony W Braithwaite
As tumour protein 53 (p53) isoforms have tumour promoting, migration and inflammatory properties, this study investigated whether p53 isoforms contributed to glioblastoma progression. The expression levels of full-length TP53α (TAp53α) and six TP53 isoforms were quantitated by RT-qPCR in 89 glioblastomas and correlated with TP53 mutation status, tumour-associated macrophage content and various immune cell markers. Elevated levels of Δ133p53β mRNA characterised glioblastomas with increased CD163-positive macrophages and wild-type TP53...
June 10, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29867974/programmed-cell-death-protein-1-pdl1-interaction-prevents-heart-damage-in-chronic-trypanosoma-cruzi-infection
#4
Raíssa Fonseca, Rafael Moysés Salgado, Henrique Borges da Silva, Rogério Silva do Nascimento, Maria Regina D'Império-Lima, José Maria Alvarez
Chagas disease is a neglected parasitic infection that affects around six to seven million people, mainly in Latin America. About 30-35% of infected people present chronic Chagas cardiomyopathy (CCC), which eventually leads to death. This condition is characterized by local parasite persistence and leukocyte infiltration. In a murine model of CCC, we observed that among infiltrating leukocytes, CD4+ and CD8+ T cells were in higher frequency in the heart of chronically infected mice, although elevated expression of the regulatory molecules programmed cell death protein 1 (PD1) and PDL1 suggested these cells could be inhibited...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29776373/metabolic-therapy-with-peg-arginase-induces-a-sustained-complete-remission-in-immunotherapy-resistant-melanoma
#5
Carmela De Santo, Paul Cheng, Andrew Beggs, Sharon Egan, Alberto Bessudo, Francis Mussai
BACKGROUND: Metastatic melanoma is an aggressive skin cancer with a poor prognosis. Current treatment strategies for high-stage melanoma are based around the use of immunotherapy with immune checkpoint inhibitors such as anti-PDL1 or anti-CTLA4 antibodies to stimulate anti-cancer T cell responses, yet a number of patients will relapse and die of disease. Here, we report the first sustained complete remission in a patient with metastatic melanoma who failed two immunotherapy strategies, by targeting tumour arginine metabolism...
May 18, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29760833/synchronous-presence-of-egfr-alk-driver-mutations-along-with-pd-l1-overexpression-in-a-resected-early-stage-non-small-cell-lung-cancer-a-case-report-and-review-of-literature
#6
Nishitha Thumallapally, Sara Parylo, Adarsh Vennepureddy, Uroosa Ibrahim, Alisa Sokoloff
Treatment of lung cancer has been revolutionized with development of drugs that target key driver mutations and immune checkpoints. Until recently, it was believed that these driver mutations are mutually exclusive. However, few reports have emerged citing the presence of both mutations either synchronously or metachronously. We describe a case report of lung adenocarcinoma harboring two driver mutations in the same tumor cells as well as exhibiting high PDL1 expression. We further discuss the possible association of these driver mutations with PDL1 expression...
April 2018: World Journal of Oncology
https://www.readbyqxmd.com/read/29758196/temozolomide-combined-with-pd-1-antibody-therapy-for-mouse-orthotopic-glioma-model
#7
Bailing Dai, Na Qi, Junchao Li, Guilong Zhang
PURPOSE: Temozolomide (TMZ) is the most frequent adjuvant chemotherapy drug in gliomas. PDL1 expresses on various tumors, including gliomas, and anti-PD-1 antibodies have been approved for treating some tumors by FDA. This study was to evaluate the therapeutical potential of combined TMZ with anti-PD-1 antibody therapy for mouse orthotopic glioma model. METHODS: We performed C57BL/6 mouse orthotopic glioma model by stereotactic intracranial implantation of glioma cell line GL261, mice were randomly divided into four groups: (1) control group; (2) TMZ group; (3) anti-PD-1 antibody group; (4) TMZ combined with anti-PD-1 antibody group...
July 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29756285/evolution-of-a-rapid-onsite-evaluation-rose-service-for-endobronchial-ultrasound-guided-ebus-fine-needle-aspiration-fna-cytology-in-a-uk-hospital-a-7-year-audit
#8
Tracey Stevenson, Manish Powari, Christopher Bowles
OBJECTIVE: Endobronchial ultrasound fine needle aspiration (EBUS FNA) is a well-established procedure for the diagnosis and staging of lung cancer. We review our provision of this service at the Royal Devon and Exeter NHS Foundation Trust and the role of rapid onsite evaluation (ROSE) with the increasing demand for molecular markers in this era of personalized medicine. METHODS: A review of the changes in the Endoscopy clinic over the 7 years from the introduction of EBUS at the end of 2010 until 2017 was carried out...
May 13, 2018: Diagnostic Cytopathology
https://www.readbyqxmd.com/read/29721379/increased-immune-infiltration-and-chemokine-receptor-expression-in-head-and-neck-epithelial-tumors-after-neoadjuvant-immunotherapy-with-the-irx-2-regimen
#9
Neil L Berinstein, Michael McNamara, Ariane Nguyen, James Egan, Gregory T Wolf
IRX-2 is an injectable cancer immunotherapy composed of cytokines purified from stimulated normal-donor peripheral blood mononuclear cells. In a phase 2a trial (n = 27), neoadjuvant IRX-2 significantly increased lymphocyte infiltration (LI) into resected head and neck tumors and was associated with changes in fibrosis and necrosis. Event-free survival was 65% at 2 years, and overall survival 65% at 5 years. Overall survival was longer for patients with LI greater versus lower than the median. This substudy of the mechanisms responsible for the increase in LI with neoadjuvant IRX-2 employed multiplex immunohistochemistry (IHC) and transcriptome analysis to interrogate matched pre- and post-treatment tumor specimens from 7 available phase 2a trial patients...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721371/complimentary-mechanisms-of-dual-checkpoint-blockade-expand-unique-t-cell-repertoires-and-activate-adaptive-anti-tumor-immunity-in-triple-negative-breast-tumors
#10
Erika J Crosby, Junping Wei, Xiao Yi Yang, Gangjun Lei, Tao Wang, Cong-Xiao Liu, Pankaj Agarwal, Alan J Korman, Michael A Morse, Kenneth Gouin, Simon R V Knott, H Kim Lyerly, Zachary C Hartman
Triple-negative breast cancer (TNBC) is an aggressive and molecularly diverse breast cancer subtype typified by the presence of p53 mutations (∼80%), elevated immune gene signatures and neoantigen expression, as well as the presence of tumor infiltrating lymphocytes (TILs). As these factors are hypothesized to be strong immunologic prerequisites for the use of immune checkpoint blockade (ICB) antibodies, multiple clinical trials testing single ICBs have advanced to Phase III, with early indications of heterogeneous response rates of <20% to anti-PD1 and anti-PDL1 ICB...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29717480/genetic-features-of-multicentric-multifocal-intramucosal-gastric-carcinoma
#11
Aya Mizuguchi, Atsushi Takai, Takahiro Shimizu, Tomonori Matsumoto, Ken Kumagai, Shin'ichi Miyamoto, Hiroshi Seno, Hiroyuki Marusawa
Chronic gastritis caused by Helicobacter pylori (H. pylori) infection could lead to the development of gastric cancer. The finding that multiple gastric cancers can develop synchronously and/or metachronously suggests the development of field cancerization in chronically inflamed, H. pylori-infected gastric mucosa. The genetic basis of multiple tumorigenesis in the inflamed stomach, however, is not well understood. In this study, we analyzed the microsatellite instability (MSI) status and copy number aberrations (CNAs) of 41 multiple intramucosal early gastric cancers that synchronously or metachronously developed in 19 patients with H...
May 1, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29692678/association-of-genetic-variants-of-pd1-with-recurrent-pregnancy-loss
#12
Yuko Hayashi, Takeshi Nishiyama, Masahiro Nakatochi, Shugo Suzuki, Satoru Takahashi, Mayumi Sugiura-Ogasawara
Purpose: Programmed cell death 1 (PD1) and PD ligand 1 (PDL1) are speculated to have an important role in maintaining a normal pregnancy and there are also a few reports of an association between the single-nucleotide polymorphisms (SNPs) of PD1 or PDL1 and diseases in humans. The association was examined between the polymorphisms of PD1 , PDL1 , CTLA4 and recurrent pregnancy loss (RPL). Methods: The study group consisted of 243 women with two or more pregnancy losses and 176 parous women...
April 2018: Reproductive Medicine and Biology
https://www.readbyqxmd.com/read/29669244/better-together-b7s1-checkpoint-blockade-synergizes-with-anti-pd1
#13
Melissa A Meyer, David G DeNardo
T cell checkpoint blockades can produce durable clinical responses, but only some patients and cancer types respond. In this issue of Immunity, Li et al. (2018) show B7S1-B7S1R signaling additionally regulates CD8+ T cell responses by working with the PD1-PDL1 checkpoint to block anti-tumor immunity.
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29668679/similarities-and-differences-between-helminth-parasites-and-cancer-cell-lines-in-shaping-human-monocytes-insights-into-parallel-mechanisms-of-immune-evasion
#14
Prakash Babu Narasimhan, Leor Akabas, Sameha Tariq, Naureen Huda, Sasisekhar Bennuru, Helen Sabzevari, Robert Hofmeister, Thomas B Nutman, Roshanak Tolouei Semnani
A number of features at the host-parasite interface are reminiscent of those that are also observed at the host-tumor interface. Both cancer cells and parasites establish a tissue microenvironment that allows for immune evasion and may reflect functional alterations of various innate cells. Here, we investigated how the phenotype and function of human monocytes is altered by exposure to cancer cell lines and if these functional and phenotypic alterations parallel those induced by exposure to helminth parasites...
April 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29650750/braf-and-mek-inhibitors-increase-pd1-positive-melanoma-cells-leading-to-a-potential-lymphocyte-independent-synergism-with-anti-pd1-antibody
#15
Martina Sanlorenzo, Igor Vujic, Arianna Floris, Mauro Novelli, Loretta Gammaitoni, Lidia Giraudo, Marco Macagno, Valeria Leuci, Ramona Rotolo, Chiara Donini, Marco Basiricò, Pietro Quaglino, Maria Teresa Fierro, Silvia Giordano, Maria Sibilia, Fabrizio Carnevale-Schianca, Massimo Aglietta, Dario Sangiolo
PURPOSE: BRAF and MEK inhibitors (BRAF/MEKi) favor melanoma-infiltrating lymphocytes, providing the rationale for current combinatorial trials with anti-PD1 antibody. A portion of melanoma cells may express PD1, and anti-PD1 antibody could have a direct anti-tumor effect. Here, we explore if BRAF/MEKi modulate rates of PD1+ melanoma cells, supporting an additional - lymphocyte-independent - basis for their therapeutic combination with anti-PD1 antibody. EXPERIMENTAL DESIGN: With data mining and flow cytometry, we assessed PD1, PDL1/2 expression on melanoma cell lines (CCLE, N=61; validation cell lines, N=7) and melanoma tumors (TCGA, N=214)...
April 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29645384/liquid-biopsy-zur-%C3%A3-berwachung-von-melanompatienten
#16
REVIEW
Maria Rita Gaiser, Nikolas von Bubnoff, Christoffer Gebhardt, Jochen Sven Utikal
In den letzten sechs Jahren wurden verschiedene innovative systemische Therapien zur Behandlung des metastasierten malignen Melanoms (MM) entwickelt. Die konventionelle Chemotherapie wurde durch neuartige Primärtherapien abgelöst, darunter systemische Immuntherapien (Anti-CTLA4- und Anti-PD1-Antikörper; Zulassung von Anti-PDL1-Antikörpern erwartet) und Therapien, die gegen bestimmte Mutationen gerichtet sind (BRAF, NRAS und c-KIT). Daher stehen die behandelnden Ärzte neuen Herausforderungen gegenüber, beispielsweise der Stratifizierung von Patienten für geeignete Behandlungen und der Überwachung von Langzeit-Respondern auf Progression...
April 2018: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/29615076/use-of-the-tumor-infiltrating-cd8-to-foxp3-lymphocyte-ratio-in-predicting-treatment-responses-to-combination-therapy-with-pertuzumab-trastuzumab-and-docetaxel-for-advanced-her2-positive-breast-cancer
#17
Koji Takada, Shinichiro Kashiwagi, Wataru Goto, Yuka Asano, Katsuyuki Takahashi, Tsutomu Takashima, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: The trastuzumab, pertuzumab, and docetaxel (TPD) regimen is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer. Monitoring the host microenvironments in cancer plays a significant role in predicting prognoses and curative effects. It is important to clarify the role of immune related gene expression in tumor-infiltrating lymphocytes in the tumor microenvironment. In this study, we evaluated the impact of chemotherapy with a TPD regimen, on immune micro environments in HER2-positive breast cancer using immune related proteins as indicators...
April 3, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29598887/expression-of-programmed-cell-death-1-programmed-cell-death-ligand-1-in-the-tumor-microenvironments-of-primary-gastrointestinal-diffuse-large-b-cell-lymphomas
#18
Yang Liu, Jing Ma, Kangjie Yu, Mingyang Li, Fang Liu, Qingguo Yan, Zhe Wang, Shuangping Guo
BACKGROUND: Gastrointestinal diffuse large B cell lymphoma (GI DLBCL) is the most common gastrointestinal lymphoma. However, there has not been a comprehensive investigation into the expression patterns of programmed cell death 1 (PD-1) and programmed cell death ligand 1(PD-L1) in GI DLBCL tissues. METHODS: PD-1 protein expression in tumor-infiltrating lymphocytes (TILs) was evaluated by immunohistochemical staining, and expression of PD-L1 was evaluated by using PD-L1/PAX5 immunohistochemical double staining in 92 GI DLBCL specimens...
April 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29564225/mechanisms-of-immune-evasion-and-immune-modulation-by-lymphoma-cells
#19
REVIEW
Thomas Menter, Alexandar Tzankov
Purpose: Targeting cancer cells by modulating the immune system has become an important new therapeutic option in many different malignancies. Inhibition of CTLA4/B7 and PD1/PDL1 signaling is now also being investigated and already successfully applied to various hematologic malignancies. Methods: A literature review of PubMed and results of our own studies were compiled in order to give a comprehensive overview on this topic. Results: We elucidate the pathophysiological role of immunosuppressive networks in lymphomas, ranging from changes in the cellular microenvironment composition to distinct signaling pathways such as PD1/PDL1 or CTLA4/B7/CD28...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29556041/cancer-associated-fibroblasts-induce-pdl1-neutrophils-through-the-il6-stat3-pathway-that-foster-immune-suppression-in-hepatocellular-carcinoma
#20
Yusheng Cheng, Hui Li, Yinan Deng, Yan Tai, Kaining Zeng, Yingcai Zhang, Wei Liu, Qi Zhang, Yang Yang
Emerging evidence indicate that cancer-associated fibroblasts (CAFs) affect tumor progression by reshaping the tumor microenvironment. Neutrophils are prominent components of solid tumors and important in cancer progression. Whether the phenotype and function of neutrophils in hepatocellular carcinoma (HCC) are influenced by CAFs is not well understood. Herein, we investigated the effect of HCC-derived CAFs (HCC-CAFs) on the neutrophils and explored the biological role of this effect. We found that HCC-CAFs induced chemotaxis of neutrophils and protected them from spontaneous apoptosis...
March 19, 2018: Cell Death & Disease
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