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pd-1 and cancer

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https://www.readbyqxmd.com/read/28550712/combined-immune-checkpoint-blockade-anti-pd-1-anti-ctla-4-evaluation-and-management-of-adverse-drug-reactions
#1
REVIEW
Jessica C Hassel, Lucie Heinzerling, Jens Aberle, Oliver Bähr, Thomas K Eigentler, Marc-Oliver Grimm, Victor Grünwald, Jan Leipe, Niels Reinmuth, Julia K Tietze, Jörg Trojan, Lisa Zimmer, Ralf Gutzmer
Combined immune checkpoint blockade (ICB) provides unprecedented efficacy gains in numerous cancer indications, with PD-1 inhibitor nivolumab plus CTLA-4 inhibitor ipilimumab in advanced melanoma as first-ever approved therapies for combined ICB. However, gains in efficacy must be balanced against a higher frequency and severity of adverse drug reactions (ADR). Because delays in diagnosis and management might result in symptom worsening and further complications, clinicians shall be well trained to identify ADR promptly and monitor patients adequately...
May 18, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28550051/pd-1-expression-on-tams-suppresses-tumor-cell-phagocytosis
#2
(no author information available yet)
PD-1/PD-L1 blockade increases TAM phagocytosis of tumor cells to extend survival in mouse cancer models.
May 26, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28549836/heterogeneity-of-tumor-and-immune-cell-pd-l1-expression-and-lymphocyte-counts-in-surgical-nsclc-samples
#3
David Casadevall, Sergi Clavé, Álvaro Taus, Max Hardy-Werbin, Pedro Rocha, Marta Lorenzo, Silvia Menéndez, Marta Salido, Joan Albanell, Lara Pijuan, Edurne Arriola
BACKGROUND: Immune-checkpoint inhibitors against programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) have shown remarkable therapeutic activity in non-small-cell lung cancer (NSCLC). However, biomarker-based patient selection remains a challenge. Our aim was to assess the heterogeneity of various immune markers between different tumor areas of surgically resected NSCLC specimens. MATERIALS AND METHODS: We included 94 adenocarcinoma (ADC) and 50 squamous cell carcinoma (SCC) specimens...
May 4, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28549039/paired-comparison-of-pd-l1-expression-on-cytologic-and-histologic-specimens-from-malignancies-in-the-lung-assessed-with-pd-l1-ihc-28-8pharmdx-and-pd-l1-ihc-22c3pharmdx
#4
Birgit G Skov, Torsten Skov
BACKGROUND: Programmed cell death ligand-1 (PD-L1) expression is a predictive biomarker for anti-PD-1 immunotherapy in non-small cell lung cancer. Different immunohistochemistry (IHC) assays have been developed on histologic material with different cutoffs for positivity. More than one third of the patients are diagnosed on cytology alone. We hypothesized that cytologic cell block material is suitable for PD-L1 analysis. MATERIALS AND METHODS: Eighty-six paired samples of malignancies from the lung where cytologic cell block and histologic material were available from the same lesion were stained with PD-L1 IHC 28-8pharmDx and PD-L1 IHC 22C3pharmDx...
May 25, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28547910/impact-of-delayed-gastric-emptying-following-pancreaticoduodenectomy-on-survival
#5
Yasuro Futagawa, Masaru Kanehira, Kenei Furukawa, Hiroaki Kitamura, Seiya Yoshida, Teruyuki Usuba, Takeyuki Misawa, Tomoyoshi Okamoto, Katsuhiko Yanaga
BACKGROUND: Delayed gastric emptying (DGE), a common postoperative complication of pancreaticoduodenectomy (PD), is not considered a life-threatening complication. In this study, we analyzed the risk factors for DGE and its impact on long-term prognosis. METHODS: We analyzed 383 patients who underwent PD between 2003 and 2010, dividing them into two groups according to DGE grade as defined by the International Study Group of Pancreatic Surgery: 243 without DGE (Non-DGE Group) and 140 with DGE of any grade (DGE Group)...
May 26, 2017: Journal of Hepato-biliary-pancreatic Sciences
https://www.readbyqxmd.com/read/28546884/in-vivo-and-in-situ-programming-of-tumor-immunity-by-combining-oncolytics-and-pd-1-immune-checkpoint-blockade
#6
Eric Bartee, Zihai Li
Blockade of the programmed cell death protein 1 (PD1) pathway is clinically effective against human cancers. Although multiple types of malignancies have been shown to respond to PD1 agents, only a small percentage of patients typically benefit from this treatment. In addition, PD1 therapy often causes serious immune-related adverse events. A recent study demonstrated that local, intra-tumoral, administration of modified oncolytic myxoma virus which expresses a truncated version of the PD1 protein resulted in both increased efficacy and reduced toxicity in a clinically relevant melanoma model...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28546465/quantitative-mass-spectrometry-analysis-of-pd-l1-protein-expression-n-glycosylation-and-expression-stoichiometry-with-pd-1-and-pd-l2-in-human-melanoma
#7
Carlos A Morales-Betanzos, Hyoungjoo Lee, Paula I Gonzalez-Ericsson, Justin M Balko, Douglas B Johnson, Lisa J Zimmerman, Daniel C Liebler
Quantitative assessment of key proteins that control the tumor-immune interface is one of the most formidable analytical challenges in immunotherapeutics. We developed a targeted mass spectrometry (MS) platform to quantify programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas. PD-L1 abundance ranged 50-fold, from approximately 0.03 to 1.5 fmol/microgram protein and the PRM data were largely concordant with total PD-L1-positive cell content, as analyzed by immunohistochemistry (IHC) with the E1L3N antibody...
May 25, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28545581/increased-serum-level-of-soluble-interleukin-2-receptor-is-associated-with-a-worse-response-of-metastatic-clear-cell-renal-cell-carcinoma-to-interferon-alpha-and-sequential-vegf-targeting-therapy
#8
Akinori Nukui, Akinori Masuda, Hideyuki Abe, Kyoko Arai, Ken-Ichiro Yoshida, Takao Kamai
BACKGROUND: Renal cell carcinoma (RCC) is a tumor with immunogenic properties. Soluble interleukin-2 receptor (sIL-2R) has a role in T cell activation and may be important for immune regulation in various conditions, including infections, transplantation rejection, autoimmune inflammatory states, and cancer. We investigated the prognostic value of the serum sIL-2R level in patients with metastatic RCC receiving IFN-alpha and vascular endothelial growth factor (VEGF)-targeting therapy...
May 25, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28545567/cancer-immunotherapy-by-targeting-immune-checkpoints-mechanism-of-t-cell-dysfunction-in-cancer-immunity-and-new-therapeutic-targets
#9
REVIEW
Hwei-Fang Tsai, Ping-Ning Hsu
Immune checkpoints or coinhibitory receptors, such as cytotoxic T lymphocyte antigen (CTLA)-4 and programmed death (PD)-1, play important roles in regulating T cell responses, and they were proven to be effective targets in treating cancer. In chronic viral infections and cancer, T cells are chronically exposed to persistent antigen stimulation. This is often associated with deterioration of T cell function with constitutive activation of immune checkpoints, a state called 'exhaustion', which is commonly associated with inefficient control of tumors and persistent viral infections...
May 25, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28544589/methionine-tumor-starvation-by-erythrocyte-encapsulated-methionine-gamma-lyase-activity-controlled-with-per-os-vitamin-b6
#10
Fabien Gay, Karine Aguera, Karine Sénéchal, Angie Tainturier, Willy Berlier, Delphine Maucort-Boulch, Jérôme Honnorat, Françoise Horand, Yann Godfrin, Vanessa Bourgeaux
Erymet is a new therapy resulting from the encapsulation of a methionine gamma-lyase (MGL; EC number 4.4.1.11) in red blood cells (RBC). The aim of this study was to evaluate erymet potential efficacy in methionine (Met)-dependent cancers. We produced a highly purified MGL using a cGMP process, determined the pharmacokinetics/pharmacodynamics (PK/PD) properties of erymet in mice, and assessed its efficacy on tumor growth prevention. Cytotoxicity of purified MGL was tested in six cancer cell lines. CD1 mice were injected with single erymet product supplemented or not with vitamin B6 vitamer pyridoxine (PN; a precursor of PLP cofactor)...
May 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28542574/combination-therapy-of-cancer-with-cancer-vaccine-and-immune-checkpoint-inhibitors-a-mathematical-model
#11
Xiulan Lai, Avner Friedman
In this paper we consider a combination therapy of cancer. One drug is a vaccine which activates dendritic cells so that they induce more T cells to infiltrate the tumor. The other drug is a checkpoint inhibitor, which enables the T cells to remain active against the cancer cells. The two drugs are positively correlated in the sense that an increase in the amount of each drug results in a reduction in the tumor volume. We consider the question whether a treatment with combination of the two drugs at certain levels is preferable to a treatment by one of the drugs alone at 'roughly' twice the dosage level; if that is the case, then we say that there is a positive 'synergy' for this combination of dosages...
2017: PloS One
https://www.readbyqxmd.com/read/28539588/cooperation-of-oncolytic-herpes-virotherapy-and-pd-1-blockade-in-murine-rhabdomyosarcoma-models
#12
Chun-Yu Chen, Pin-Yi Wang, Brian Hutzen, Les Sprague, Hayley M Swain, Julia K Love, Joseph R Stanek, Louis Boon, Joe Conner, Timothy P Cripe
Oncolytic virotherapy is an effective immunotherapeutic approach for cancer treatment via a multistep process including direct tumor cell lysis, induction of cytotoxic or apoptosis-sensitizing cytokines and promotion of antitumor T cell responses. Solid tumors limit the effectiveness of immunotherapeutics in diverse ways such as secretion of immunosuppressive cytokines and expression of immune inhibitory ligands to inhibit antitumor T cell function. Blocking programmed cell death protein (PD)-1 signaling, which mediates T cell suppression via engagement of its inhibitory ligands, PD-L1 or PD-L2, is of particular interest due to recent successes in many types of cancer...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539555/inter-patient-and-intra-tumor-heterogeneity-in-the-sensitivity-to-tumor-targeted-immunity-in-colorectal-cancer
#13
Tsubasa Miyauchi, Tomonori Yaguchi, Yutaka Kawakami
  Efficacy of immune checkpoint inhibitors such as PD-1 antibody for colorectal cancer remains to be proved except in microsatellite-instability-high (MSI-H) cases. While the objective response rate of MSI-H cases was 40%, that of microsatellite-stable (MSS) cases was 0%, showing that response rate to immune checkpoint inhibitors varies even among the microsatellite status. Some possible mechanisms that confer each patient variation in the response to immunotherapy should be considered. We focused on the combination of inter-patient heterogeneity and intra-tumor heterogeneity as a determining factor of immune reaction...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28539467/b7-h3-expression-in-nsclc-and-its-association-with-b7-h4-pd-l1-and-tumor-infiltrating-lymphocytes
#14
Mehmet Altan, Vasiliki Pelekanou, Kurt A Schalper, Maria I Toki, Patricia Gaule, Konstantinos N Syrigos, Roy S Herbst, David L Rimm
Background and Purpose: <p>The immune checkpoint PD-1 and its receptor B7-H1 (PD-L1) are successful therapeutic targets in cancer but less is known about other B7 family members.  Here, we determined the expression level of B7-H3 protein in non-small cell lung cancer (NSCLC) and evaluated its association with tumor infiltrating lymphocytes (TILs), PD-L1, B7-H4 and major clinico-pathological characteristics is in 3 NSCLC cohorts.</p> <p>Experimental design:</p> <p>We used multiplexed automated quantitative immunofluorescence (QIF) to assess the levels of B7-H3, PD-L1, B7-H4 and TILs in 634 NSCLC cases with validated antibodies...
May 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28539123/multilevel-genomics-of-colorectal-cancers-with-microsatellite-instability-clinical-impact-of-jak1-mutations-and-consensus-molecular-subtype-1
#15
Anita Sveen, Bjarne Johannessen, Torstein Tengs, Stine A Danielsen, Ina A Eilertsen, Guro E Lind, Kaja C G Berg, Edward Leithe, Leonardo A Meza-Zepeda, Enric Domingo, Ola Myklebost, David Kerr, Ian Tomlinson, Arild Nesbakken, Rolf I Skotheim, Ragnhild A Lothe
BACKGROUND: Approximately 15% of primary colorectal cancers have DNA mismatch repair deficiency, causing a complex genome with thousands of small mutations-the microsatellite instability (MSI) phenotype. We investigated molecular heterogeneity and tumor immunogenicity in relation to clinical endpoints within this distinct subtype of colorectal cancers. METHODS: A total of 333 primary MSI+ colorectal tumors from multiple cohorts were analyzed by multilevel genomics and computational modeling-including mutation profiling, clonality modeling, and neoantigen prediction in a subset of the tumors, as well as gene expression profiling for consensus molecular subtypes (CMS) and immune cell infiltration...
May 24, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28538872/melanoma-tumor-microenvironment-and-new-treatments
#16
Mara Huffenbaecher Giavina-Bianchi, Pedro Francisco Giavina-Bianchi, Cyro Festa
In the recent past years, many discoveries in the tumor microenvironment have led to changes in the management of melanoma and it is rising up hopes, specially, to those in advanced stages. FDA approved seven new drugs from 2011 to 2014. They are: Vemurafenib, Dabrafenib and Trametinib, kinases inhibitors used for patients that have BRAFV600E mutation; Ipilimumab (anti-CTLA4), Pembrolizumab (anti-PD-1) and Nivolumab (anti-PD-1), monoclonal antibodies that stimulate the immune system; and Peginterferon alfa-2b, an anti-proliferative cytokine used as adjuvant therapy...
March 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/28538431/immunotherapy-for-lung-cancer-targeting-the-pd-1-pathway
#17
Sam Vafadar
Lung cancer is the third most common cancer in the United States and the top cause of cancer-related mortality in men and women. Despite advances in chemotherapy, molecular therapies, and CT screening, overall survival remains dismal. Additional options and a new treatment paradigm are needed. This article focuses on immunotherapy, a promising new approach targeted at the PD-1 inhibition pathway.
June 2017: JAAPA: Official Journal of the American Academy of Physician Assistants
https://www.readbyqxmd.com/read/28537924/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#18
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537896/5t4-oncofoetal-glycoprotein-an-old-target-for-a-novel-prostate-cancer-immunotherapy
#19
Federica Cappuccini, Emily Pollock, Stephen Stribbling, Adrian V S Hill, Irina Redchenko
The tumour-associated antigen 5T4 is an attractive target for cancer immunotherapy. However to date, reported 5T4-specific cellular immune responses induced by various immunisation platforms have been largely weak or non-existent. In the present study, we have evaluated a heterologous prime boost regime based on the simian adenovirus ChAdOx1 and modified vaccinia virus Ankara (MVA) expressing 5T4 for immunogenicity and tumour protective efficacy in a mouse cancer model. Vaccination-induced immune responses were strong, durable and attributable primarily to CD8+ T cells...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537889/immune-signature-of-metastatic-breast-cancer-identifying-predictive-markers-of-immunotherapy-response
#20
Ji-Yeon Kim, Eunjin Lee, Kyunghee Park, Woong-Yang Park, Hae Hyun Jung, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
In breast cancer (BC), up to 10-20% patients were known to have clinical benefit with immune checkpoint inhibitors, and biomarkers are needed for optimal use of this multi-potential therapeutic strategy. Accordingly, we conducted an experiment to identify expression of genes associated with immune checkpoints that represent potential targets of cancer immunotherapy. We performed whole-transcriptome sequencing and whole-exome sequencing using 37 refractory BC specimens. In the immune pathway gene set expression analysis, we found that HER2 expression and previous taxane treatment were positively correlated with high expression of immune gene set expression (p = 0...
May 7, 2017: Oncotarget
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