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PD1 cancer

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https://www.readbyqxmd.com/read/29344269/early-and-partial-reduction-in-cd4-foxp3-regulatory-t-cells-during-colitis-associated-colon-cancer-induces-cd4-and-cd8-t-cell-activation-inhibiting-tumorigenesis
#1
Jonadab E Olguín, Itzel Medina-Andrade, Emmanuel Molina, Armando Vázquez, Thalia Pacheco-Fernández, Rafael Saavedra, Carlos Pérez-Plasencia, Yolanda I Chirino, Felipe Vaca-Paniagua, Luis E Arias-Romero, Emma B Gutierrez-Cirlos, Sonia A León-Cabrera, Miriam Rodriguez-Sosa, Luis I Terrazas
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in women and the third in men in North America and Europe. CRC is associated with inflammatory responses in which intestinal pathology is caused by different cell populations including a T cell dysregulation that concludes in an imbalance between activated T (Tact) and regulatory T (Treg) cells. Treg cells are CD4+Foxp3+ cells that actively suppress pathological and physiological immune responses, contributing to the maintenance of immune homeostasis...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29339375/tusc2-immunogene-synergizes-with-anti-pd1-through-enhanced-proliferation-and-infiltration-of-natural-killer-cells-in-syngeneic-kras-mutant-mouse-lung-cancer-models
#2
Ismail M Meraz, Mourad Majidi, Xiaobo Cao, Heather Lin, Lerong Li, Jing Wang, Veerabhadran Baladandayuthapani, David Rice, Boris Sepesi, Lin Ji, Jack A Roth
Expression of the multikinase inhibitor encoded by tumor suppressor gene TUSC2 (also known as FUS1) is lost or decreased in non-small cell lung carcinoma (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor regression in clinical trials. Because of the role of TUSC2 in regulating immune cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in combination with anti-PD-1 in two Kras-mutant syngeneic mouse lung cancer models. TUSC2 alone significantly reduced tumor growth and prolonged survival compared with anti-PD-1...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29337311/dinaciclib-induces-immunogenic-cell-death-and-enhances-anti-pd-1-mediated-tumor-suppression
#3
Dewan Md Sakib Hossain, Sarah Javaid, Mingmei Cai, Chunsheng Zhang, Anandi Sawant, Marlene Hinton, Manjiri Sathe, Jeff Grein, Wendy Blumenschein, Elaine M Pinheiro, Alissa Chackerian
Blockade of the checkpoint inhibitor programmed death 1 (PD1) has demonstrated remarkable success in the clinic for the treatment of cancer; however, a majority of tumors are resistant to anti-PD1 monotherapy. Numerous ongoing clinical combination therapy studies will likely reveal additional therapeutics that complement anti-PD1 blockade. Recent studies found that immunogenic cell death (ICD) improves T cell responses against different tumors, thus indicating that ICD may further augment antitumor immunity elicited by anti-PD1...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29336717/pd1-protein-expression-in-tumor-infiltrated-lymphocytes-rather-than-pdl1-in-tumor-cells-predicts-survival-in-triple-negative-breast-cancer
#4
Xinyu Ren, Huanwen Wu, Junliang Lu, Yuhan Zhang, Yufeng Luo, Qianqian Xu, Songjie Shen, Zhiyong Liang
ABASTRACT To determine PD1/PDL1 expression status in triple-negative breast cancer (TNBC) at both protein and mRNA levels, and to analyze the relationship between their expression and clinical parameters of the TNBC patients. Immunohistochemistry and RNAscope were used to semi quantitively evaluate PD1/PDL1 protein and mRNA expression in 195 TNBC cases on tissue microarrays. Tumor infiltrating lymphocyte (TILs) abundance was assessed using hematoxylin-eosin staining.Both tumor cells and TILs expressed PDL1...
January 16, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29336431/anti-pd1-in-the-wonder-gut-land
#5
Marie Vetizou, Giorgio Trinchieri
After the initial success of cancer immunotherapy using immune checkpoint blockers, the challenge is to understand why only a minority of patients respond to the therapy and to increase the rate of response. Three recent papers now report that the gut microbiota modulates the response to anti-PD1 therapy in patients with epithelial cancers or melanoma.
January 16, 2018: Cell Research
https://www.readbyqxmd.com/read/29332341/association-of-the-combined-parameters-including-the-frequency-of-primary-cilia-cd8-tumor-infiltrating-lymphocytes-and-pd-1-expression-with-the-outcome-in-intestinal-cancer
#6
Josef Dvorak, Dimitar Hadzi Nikolov, Ladislav Dusek, Alzbeta Filipova, Igor Richter, David Buka, Ales Ryska, Jaroslav Mokry, Stanislav Filip, Bohuslav Melichar, Tomas Buchler, Jitka Abrahamova
PURPOSE: Primary cilium (PC) is considered to be a functional homologue of the immune synapse. Microtubule structures, PC of cancer associated fibroblasts and immune synapses between cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) and cancer cells, are regularly found in varying amounts in the microenvironment of solid tumors. The purpose of this study was to find out the potential association and combined prognostic significance of the frequency of PC, PD-1 and CD8+ TILs in patients with intestinal cancer...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29327065/blood-predictive-biomarkers-for-nivolumab-in-advanced-melanoma
#7
Edouard Chasseuil, Mélanie Saint-Jean, Hannah Chasseuil, Lucie Peuvrel, Gaëlle Quéreux, Jean-Michel Nguyen, Aurélie Gaultier, Emilie Varey, Amir Khammari, Brigitte Dréno
Nivolumab response rate is 40% in metastatic melanoma. Few studies have evaluated pre-treatment biomarkers predictive of response. The aim of this study was to identify potential peripheral blood biomarkers associated with survival in patients with advanced melanoma treated with nivolumab. All advanced melanoma cases treated with anti-programmed cell death protein 1 (anti-PD1) over a 3-year period in our department were identified. For each case, 9 potential blood biomarkers were identified. Bivariate and multivariate analyses, adjusted for the American Joint Committee on Cancer (AJCC) classification stage, Eastern Cooperative Oncology Group (ECOG) performance status, lactate dehydrogenase (LDH) level and failure to respond to first-line therapy, were used to test the association between biomarkers and overall survival (primary outcome) or progression-free survival (secondary outcome)...
December 20, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/29303012/blockade-of-ccr5-mediated-myeloid-derived-suppressor-cell-accumulation-enhances-anti-pd1-efficacy-in-gastric-cancer
#8
Liu Yang, Bing Wang, Jian Qin, HengHua Zhou, Adhip P N Majumdar, Fei Peng
PURPOSE: Myeloid derived suppressor cells (MDSC) play an important role in tumor immune evasion and its level significantly increased in patients with gastric cancer. Studies confirmed the associations between MDSC and various cytokines in the peripheral blood. However, little is known about the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and CCR5 level in gastric cancer. MATERIALS AND METHODS: G-MDSC and M-MDSC from the peripheral blood and tumor parenchyma were analyzed by flow cytometry...
January 5, 2018: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/29298730/cytokine-release-syndrome-after-radiation-therapy-case-report-and-review-of-the-literature
#9
Christopher A Barker, Samuel K Kim, Sadna Budhu, Konstantina Matsoukas, Anthony F Daniyan, Sandra P D'Angelo
BACKGROUND: Cytokine release syndrome (CRS) has been reported after immunologic manipulations, most often through therapeutic monoclonal antibodies. To our knowledge, CRS after radiation therapy (RT) for cancer has not been reported before. The development of unusual clinical signs and symptoms after RT led us to investigate the possibility of CRS after RT and review the medical literature on this topic. CASE PRESENTATION: A 65 year-old man with untreated chronic lymphocytic leukemia and recurrent, metastatic Merkel cell carcinoma undergoing anti-programmed death 1 (PD1) immunotherapy was referred for palliative RT to sites of progressing metastases...
January 3, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29296194/changes-in-pd-l1-expression-according-to-tumor-infiltrating-lymphocytes-of-acquired-egfr-tki-resistant-egfr-mutant-non-small-cell-lung-cancer
#10
Tae-Jung Kim, Soon Auck Hong, Okran Kim, Seung Joon Kim, Ji-Hyun Yang, Eun Kyo Joung, Jin-Hyoung Kang, Sook-Hee Hong
Backgrounds: EGFR-mutant non-small cell lung cancer (NSCLC) that developed acquired resistance to EGFR-tyrosine kinase (TKI) are potential candidates for programmed death 1 (PD1) inhibitor. Results: TPS≥1% for PD-L1 and low CD8 + TIL in post-TKI tumor showed a trend for a lower PFS of EGFR-TKIs (14.2 vs 9.9 months; P = 0.060) (cohort A). Only 2 of 22 specimens (9.1%) with an acquired EGFR exon 20 T790M mutation exhibited in post-TKI TPS≥50% for PD-L1. The degree in post-TKI tumor of PD-L1 expression was varied in 19 patients (40...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29289336/-hodgkin-lymphoma-current-and-future-therapeutic-strategies
#11
REVIEW
Anthony Turpin, Jean-Marie Michot, Emmanuelle Kempf, Renaud Mazeron, Peggy Dartigues, Angela Boros, Serge Bonnetier, Cristina Castilla-Llorente, Tereza Coman, Alina Danu, David Ghez, Sylvain Pilorge, Julia Arfi-Rouche, Laurent Dercle, Jean-Charles Soria, Patrice Carde, Vincent Ribrag, Christophe Fermé, Julien Lazarovici
Hodgkin lymphoma (HL) is a cancer that mostly affects young people, in which modern therapeutic strategies using chemotherapy and radiotherapy result in a cure rate exceeding 80%. Survivors are exposed to long-term consequences of treatments, such as secondary malignancies and cardiovascular diseases, whose mortality exceeds the one of the disease itself, with long-term follow-up. The current therapeutic strategy in HL, based on the assessment of initial risk factors, is the result of large clinical trials led by the main international cooperating groups...
December 27, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29274233/efficacy-of-anti-pd-1-on-skin-carcinomas-and-melanoma-metastases-in-an-xeroderma-pigmentosum-patient
#12
G Salomon, A Maza, S Boulinguez, C Paul, L Lamant, E Tournier, J Mazereeuw-Hautier, N Meyer
Xeroderma pigmentosum is an orphan disease of poor prognosis. We report one case of parallel efficacy with anti-PD-1 antibody on both melanoma and skin carcinoma in a xeroderma pigmentosum patient. A 17-year old patient presented with metastatic melanoma and multiple non melanoma skin cancers. He was treated with pembrolizumab, a monoclonal anti-PD-1 antibody, at the dose of 2mg/Kg 3 weeks apart. Parallel therapeutic efficacy of anti-PD1 was observed in metastatic melanoma and skin carcinomas, and maintained at week 24...
December 23, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29247829/pd-1-modulates-radiation-induced-cardiac-toxicity-through-cytotoxic-t-lymphocytes
#13
Shisuo Du, Lin Zhou, Gregory S Alexander, Kyewon Park, Lifeng Yang, Nadan Wang, Xinliang Ma, Yajing Wang, Adam P Dicker, Bo Lu
INTRODUCTION: Combined immune checkpoint blockade has led to rare autoimmune complications, such as fatal myocarditis. Recent approvals of several anti-PD1 drugs for lung cancer treatment prompted ongoing clinical trials that directly combine PD-1 inhibitors with thoracic radiotherapy for locally advanced lung cancer. Overlapping toxicities from either modality have the potential to increase the risk for radiation-induced cardiotoxicity (RICT), which is well documented among patients with HD and breast cancer...
December 13, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29241546/neutrophils-and-snail-orchestrate-the-establishment-of-a-pro-tumor-microenvironment-in-lung-cancer
#14
Julien Faget, Svenja Groeneveld, Gael Boivin, Martial Sankar, Nadine Zangger, Miguel Garcia, Nicolas Guex, Inti Zlobec, Loïc Steiner, Alessandra Piersigilli, Ioannis Xenarios, Etienne Meylan
Understanding the immune compartment of tumors facilitates the development of revolutionary new therapies. We used a Kras(G12D)-driven mouse model of lung cancer to establish an immune signature and identified a contribution of Gr1+ neutrophils to disease progression. Depletion experiments showed that Gr1+ cells (1) favor tumor growth, (2) reduce T cell homing and prevent successful anti-PD1 immunotherapy, and (3) alter angiogenesis, leading to hypoxia and sustained Snail expression in lung cancer cells. In turn, Snail accelerated disease progression and increased intratumoral Cxcl2 secretion and neutrophil infiltration...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29241019/quantitative-analysis-of-a-multiplexed-immunofluorescence-panel-in-t-cell-lymphoma
#15
Siok-Bian Ng, Shuangyi Fan, Shoa-Nian Choo, Michal Hoppe, Hoang Mai Phuong, Sanjay De Mel, Anand D Jeyasekharan
Immunohistochemistry (IHC) provides clinically useful information on protein expression in cancer cells. However, quantification of colocalizing signals using conventional IHC and visual scores is challenging. Here we describe the application of quantitative immunofluorescence in angioimmunoblastic T-cell lymphoma (AITL), a peripheral T-cell lymphoma characterized by cellular heterogeneity that impedes IHC interpretation and quantification. A multiplexed immunofluorescence (IF) panel comprising T- and B-lymphocyte markers along with T-follicular helper (TFH) markers was validated for appropriate cellular localization in sections of benign tonsillar tissue and tested in two samples of AITL, using a Vectra microscope for spectral imaging and InForm software for analysis...
December 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/29239195/-immunotherapy-of-colorectal-and-anal-carcinoma
#16
J Tomášek, I Kiss
BACKGROUND: The lower part of the digestive tract includes the large intestine, rectum and anus. Treatment algorithms of cancers in these localities have significant differences in both early and advanced stages. The vast majority of metastatic cases are incurable. A few years ago, it was generally accepted that gastrointestinal tumors are poorly immunogenic and modern immunotherapy would not work in gastrointestinal cancers. The breakthrough has become the recognition of the mismatch repair system (MMR) that affects the microsatellite instability (MSI) and its role in the development of colorectal carcinoma (CRC)...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29239193/-checkpoint-inhibitors-in-the-treatment-of-upper-gastrointestinal-tract-tumors
#17
R Obermannova
Chemotherapy prolongs overall survival (OS) in esophageal (EC) and gastric cancer (GC). Unsatisfactory results of systemic therapy initiated a search for new treatment options. In metastatic disease, a number of targeted drugs were tested; however, several phase III studies assessing receptor tyrosin kinase-related signaling pathways, such as EGFR, MET/HGF or mTOR, failed. Trastuzumab remains the only targeted drug with a known molecular predictor, which extended the OS in metastatic gastric adenocarcinoma and adenocarcinoma of esophago-gastric junction...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29228559/initial-experience-of-anti-pd1-therapy-with-nivolumab-in-advanced-hepatocellular-carcinoma
#18
Duan Feng, Xie Hui, Lu Shi-Chun, Bai Yan-Hua, Cui Li, Li Xiao-Hui, Yan Jie-Yu
Purpose: To evaluate efficacy and safety of anti-PD1 therapy with nivolumab for treatment of advanced hepatocellular carcinoma (HCC). Methods: From Jan 2016 to Jan 2017, eleven cases of HCC (average age of 51.8-year), 4 at stage B and 7 at stage C, according to Barcelona Clinic Liver Cancer staging, were treated with nivolumab. There were 4 patients with lung metastasis, 1 with portal vein tumor thrombus, 1 with abdominal metastasis and 1 with bone metastasis. The protocol was nivolumab, 3 mg/kg, on day 1, q3w...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29226090/inhibition-of-il-18-mediated-myeloid-derived-suppressor-cell-accumulation-enhances-anti-pd1-efficacy-against-osteosarcoma-cancer
#19
Ying Guan, Rui Zhang, Zhibin Peng, Daming Dong, Guojun Wei, Yansong Wang
Myeloid derived suppressor cells (MDSC) are very important in tumor immune evasion and they dramatically increased in peripheral blood of patients with osteosarcoma cancer. The association between MDSC and various cytokines has been studied in the peripheral blood. However, little is known about the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and interleukin 18 (IL-18) level in osteosarcoma tumor model and its effect on the immunotherapy. MDSC were isolated from the blood and parenchyma and analyzed in the osteosarcoma tumor model...
November 2017: Journal of Bone Oncology
https://www.readbyqxmd.com/read/29225343/advances-in-the-understanding-and-treatment-of-sepsis-induced-immunosuppression
#20
REVIEW
Fabienne Venet, Guillaume Monneret
Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Sepsis can induce acute kidney injury and multiple organ failures and represents the most common cause of death in the intensive care unit. Sepsis initiates a complex immune response that varies over time, with the concomitant occurrence of both pro-inflammatory and anti-inflammatory mechanisms. As a result, most patients with sepsis rapidly display signs of profound immunosuppression, which is associated with deleterious consequences...
December 11, 2017: Nature Reviews. Nephrology
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