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https://www.readbyqxmd.com/read/28109025/immune-regulation-by-t-regulatory-cells-in-hbv-related-inflammation-and-cancer
#1
REVIEW
Nirupama Trehanpati, Ashish Kumar Vyas
Hepatocellular carcinoma (HCC) is the leading cause of cancer death and hepatitis B virus (HBV) infection is one of the commonest causes in Asians countries. India has the second largest pool after China for hepatitis B infected subjects. HBV clearance is T cell dependent and one of the reason for T cells hypo responsiveness is due to mass production of Tregs through activation of Notch signaling, which suppressCD4/CD8 T cells. Regulatory T cells (Tregs) are important to maintain cellular homeostasis; however during viral infection increase of Tregs is inversely proportional to HBV DNA titers...
January 21, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28088309/-new-therapy-outlooks-in-hodgkin-lymphoma
#2
REVIEW
Cédric Rossi, René-Olivier Casasnovas
Classical Hodgkin lymphoma (HL) is a curable disease in 80% of advanced and 90% of localized stages. An improvement of the HL curability is still possible with the emergence of first-line therapy with a better balance between efficacy and toxicity and early identification patients with high risk of failure requiring specific treatment. 18FDG PET-CT gained a major role in the baseline staging and response assessment to HL treatment. The prognostic value of early PET-CT allowed to develop PET-CT guided therapies able to optimize the balance between efficacy and toxicity including the modulation of the chemotherapy intensity or the omission of radiotherapy for some localized diseases...
January 11, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28077434/transfer-of-allogeneic-cd4-t-cells-rescues-cd8-t-cells-in-anti-pd-l1-resistant-tumors-leading-to-tumor-eradication
#3
Ainhoa Arina, Theodore G Karrison, Eva Galka, Karin Schreiber, Ralph R Weichselbaum, Hans Schreiber
Adoptively transferred CD8(+) T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T cell-mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule K(b) needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8(+) T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months...
January 11, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28073132/hypothyroidism-in-cancer-patients-on-immune-checkpoint-inhibitors-with-anti-pd1-agents-insights-on-underlying-mechanisms
#4
M Alhusseini, J Samantray
Background: Immune therapy using monoclonal antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) for various cancers have been reported to cause thyroid dysfunction. Little is known, however, about the underlying pathogenic mechanisms and the course of hypothyroidism that subsequently develops. In this report, we use the change in thyroglobulin and thyroid antibody levels in patients on immune therapy who develop hypothyroidism to better understand its pathogenesis as well as examine the status of hypothyroidism in the long term...
January 10, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28064139/neurological-adverse-events-associated-with-immune-checkpoint-inhibitors-review-of-the-literature
#5
REVIEW
S Cuzzubbo, F Javeri, M Tissier, A Roumi, C Barlog, J Doridam, C Lebbe, C Belin, R Ursu, A F Carpentier
Immune checkpoint inhibitors (ICIs) targeting CTLA4 and PD1 constitute a promising class of cancer treatment but are associated with several immune-related disorders. We here review the literature reporting neurological adverse events (nAEs) associated with ICIs. A systematic search of literature, up to February 2016, mentioning nAEs in patients treated with ICIs was conducted. Eligible studies included case reports and prospective trials. One case seen in our ward was also added. Within the 59 clinical trials (totalling 9208 patients) analysed, the overall incidence of nAEs was 3...
January 5, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28055269/targeting-pd-1-pathway-a-new-hope-for-gastrointestinal-cancers
#6
Burak Bilgin, Mehmet An Sendur, Muhammed Bülent Akıncı, Didem Şener Dede, Bülent Yalçın
BACKGROUND: VEGF, HER2 and EGFR targeted agents are currently used in gastric, esophageal and colorectal cancers. However, treatment outcomes are still poor in most of the Gastrointestinal (GI) cancers. Immune checkpoints are one of the most promising immunotherapy approaches. In this review article, we aimed to discuss the efficacy and safety of anti-PD-1/PD-L1 therapies in GI cancers, including gastric, esophageal and colorectal cancer in the era of published or reported recent studies...
January 5, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28054961/the-in-vitro-and-in-vivo-anti-inflammatory-effects-of-a-phthalimide-ppar-%C3%AE-agonist
#7
Mingzhi Su, Jiafu Cao, Jin Huang, Sen Liu, Dong Soon Im, Jin-Wook Yoo, Jee H Jung
Previously, the authors found that 4-hydroxy-2-(4-hydroxyphenethyl) isoindoline-1,3-dione (PD1) (a phthalimide analogue) bound to and activated peroxisome proliferator-activated receptor-γ (PPAR-γ). Since PPAR-γ suppresses inflammatory responses, the present study was undertaken to investigate the anti-inflammatory effects of PD1. In lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophages, PD1 suppressed the inductions of pro-inflammatory factors, including inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase 2 (COX-2), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)...
January 4, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28054442/markers-and-function-of-human-nk-cells-in-normal-and-pathological-conditions
#8
REVIEW
Genny Del Zotto, Emanuela Marcenaro, Paola Vacca, Simona Sivori, Daniela Pende, Mariella Della Chiesa, Francesca Moretta, Tiziano Ingegnere, Maria Cristina Mingari, Alessandro Moretta, Lorenzo Moretta
Natural killer (NK) cells, the most important effectors of the Innate Lymphoid Cells (ILCs), play a fundamental role in tumor immune-surveillance, defense against viruses and, in general, in innate immune responses. NK cell activation is mediated by several activating receptors and co-receptors able to recognize ligands on virus-infected or tumor cells. To prevent healthy cells from auto-aggression, NK cells are provided with strong inhibitory receptors (KIRs and NKG2A) which recognize HLA class I molecules on target cells and, sensing their level of expression, allow killing of targets underexpressing HLA-class I...
January 5, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28031159/evolution-of-neoantigen-landscape-during-immune-checkpoint-blockade-in-non-small-cell-lung-cancer
#9
Valsamo Anagnostou, Kellie N Smith, Patrick M Forde, Noushin Niknafs, Rohit Bhattacharya, James White, Theresa Zhang, Vilmos Adleff, Jillian Phallen, Neha Wali, Carolyn Hruban, Violeta B Guthrie, Kristen Rodgers, Jarushka Naidoo, Hyunseok Kang, William H Sharfman, Christos Georgiades, Franco Verde, Peter Illei, Qing Kay Li, Edward Gabrielson, Malcolm V Brock, Cynthia A Zahnow, Stephen B Baylin, Robert Scharpf, Julie R Brahmer, Rachel Karchin, Drew M Pardoll, Victor E Velculescu
Immune checkpoint inhibitors have shown significant therapeutic responses against tumors containing increased mutation-associated neoantigen load. We have examined the evolving landscape of tumor neoantigens during the emergence of acquired resistance in non-small cell lung cancer patients after initial response to immune checkpoint blockade with anti-PD1 or anti-PD-1/anti-CTLA4 antibodies. Analyses of matched pretreatment and resistant tumors identified genomic changes resulting in loss of 7 to 18 putative mutation-associated neoantigens in resistant clones...
December 28, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/28007774/combined-kit-and-ctla-4-blockade-in-patients-with-refractory-gist-and-other-advanced-sarcomas-a-phase-ib-study-of-dasatinib-plus-ipilimumab
#10
Sandra P D'Angelo, Alexander N Shoushtari, Mary Louise Keohan, Mark A Dickson, Mrinal M Gounder, Ping Chi, Jennifer K Loo, Leigh Gaffney, Lee Schneider, Zarine Patel, Joseph P Erinjeri, Mark Bluth, Ana Sjoberg, Howard Streicher, Naoko Takebe, Li-Xuan Qin, Cristina R Antonescu, Ronald P DeMatteo, Richard D Carvajal, William D Tap
PURPOSE: A phase Ib study of dasatinib plus ipilimumab in GIST and other sarcomas was performed based on pre-clinical data demonstrating that combined KIT and CTLA-4 blockade is synergistic. EXPERIMENTAL DESIGN: A standard 3+3 design was used evaluate the safety, efficacy and immune correlates of treatment. Dose escalation cohorts received ipilimumab 10 or 3 mg/kg every 3 weeks followed by maintenance every 12 weeks with escalating doses of dasatinib (70mg daily, 100 mg daily or 70 mg twice daily)...
December 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28003307/pi3k-inhibition-reduces-mammary-tumor-growth-and-facilitates-anti-tumor-immunity-and-anti-pd1-responses
#11
Jiqing Sai, Philip Owens, Sergey V Novitiskiy, Oriana E Hawkins, Anna E Vilgelm, Jinming Yang, Tammy Sobolik-Delmaire, Nicole Lavender, Andrew C Johnson, Colt McClain, Gregory D Ayers, Mark C Kelley, Melinda Sanders, Ingrid A Mayer, Harold L Moses, Mark Boothby, Ann Richmond
PURPOSE: Metastatic breast cancers continue to elude current therapeutic strategies, including those utilizing PI3K inhibitors. Given the prominent role of PI3Kα,β in tumor growth and PI3Kγ,δ in immune cell function, we sought to determine whether PI3K inhibition altered anti-tumor immunity. EXPERIMENTAL DESIGN: The effect of PI3K inhibition on tumor growth, metastasis, and anti-tumor immune response was characterized in mouse models utilizing orthotopic implants of 4T1 or PyMT mammary tumors into syngeneic or PI3Kγ null mice, and patient-derived breast cancer xenografts in humanized mice...
December 21, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28003304/genomic-profiling-of-patient-derived-xenografts-for-lung-cancer-identifies-b2m-inactivation-impairing-immunorecognition
#12
Carolina Pereira, Pol Gimenez-Xavier, Eva Pros, Maria J Pajares, Massimo Moro, Antonio Gomez, Alejandro Navarro, Enric Condom, Sebastian Moran, Gonzalo Gómez-López, Osvaldo Graña, Miriam Rubio-Camarillo, Alex Martinez-Martí, Jun Yokota, Julian Carretero, Jose M Galbis, Ernest Nadal, David G Pisano, Gabriella Sozzi, Enriqueta Felip, Luis M Montuenga, Luca Roz, Alberto Villanueva, Montse Sanchez-Cespedes
PURPOSE: We aimed to maximize the performance of detecting genetic alterations in lung cancer (LC) using high-throughput sequencing for patient-derived xenografts (PDXs). EXPERIMENTAL DESIGN: We undertook an integrated RNA and whole-exome sequencing of 14 PDXs. We focused on the genetic and functional analysis of B2-microglobulin (B2M), a component of the HLA class-I complex. RESULTS: We identified alterations in genes involved in various functions, such as B2M involved in immunosurveillance...
December 21, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28000240/epidermal-anti-programmed-cell-death-ligand-1-expression-in-ten-associated-with-nivolumab-therapy
#13
Karina L Vivar, Maria Deschaine, Jane Messina, Jennifer M Divine, Alejandro Rabionet, Nishit Patel, Michael A Harrington, Lucia Seminario-Vidal
BACKGROUND: Nivolumab is an anti-programmed cell death receptor-1 (PD-1) antibody used in the treatment of metastatic or unresectable melanoma. Cutaneous reactions are the most common adverse events reported with these agents and are rarely severe or life-threatening. METHODS: Case report describing the clinicopathological findings of a patient with a fatal toxic epidermal necrolysis (TEN) eruption associated with use of nivolumab for treatment of metastatic melanoma...
December 21, 2016: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/27997006/-nivolumab-in-second-line-treatment-of-squamous-non-small-cell-lung-cancer
#14
Filippo De Marinis, Antonio Passaro
The treatment of non-small cell lung cancer (NSCLC) is changing dramatically in the last period, considering both non-squamous and squamous disease. In the last five years, the identification of different molecular predictive biomarker (e.g., EGFR, ALK e ROS1) and the utilize of new chemotherapy agents associated or not with antiangiogenics agents (e.g., bevacizumab and nintedanib), allowed the improvement of survival and related responses to these treatments. However, these advances, did not allow an improvement of the same endpoints in the management of NSCLC with squamous cell histology (SCC), where until very recently, docetaxel in monotherapy remained as a corner stone treatment for the second line, although associated with an unfavorable toxicity profile...
December 2016: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/27987497/-significance-of-different-t-follicular-helper-subsets-in-rheumatoid-arthritis
#15
X M Chen, J Li, X Y Zhang, Y B Jin, D Yu, X L Sun, L J Wu, J He, Z G Li
OBJECTIVE: To detect the expressions of T follicular helper (Tfh) subsets and T follicular helper effect memory (Tfhem) cells in circulation of patients with rheumatoid arthritis (RA), as well as to examine their roles in providing biomarkers for active RA. METHODS: This study enrolled 41 patients with RA, who were navely-treated or had no application of hormone and disease-modifying anti-rheumatic drugs in recent 3 months, as well as 32 healthy controls. The percentages of Tfhem (CD4(+)CXCR5(+)CCR7(low)PD1(high)) cells, Tfh (CD3(+)CD4(+)CXCR5(+)CD45RA(-)) subsets, Tfh1 (CXCR3(+)CCR6(-)Tfh),Tfh2 (CXCR3(-)CCR6(-)Tfh),and Tfh17 (CXCR3(-)CCR6(+)Tfh), were determined by flow cytometry of peripheral blood from the patients with RA and health controls...
December 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/27969531/ps01-64-effect-of-anti-pd1-therapy-on-the-incidence-of-thromboembolic-events-in%C3%A2-lung-cancer-topic-medical-oncology
#16
Aparna Hegde, Cindy Cherry, Geoff Stroud, Sulochana Cherukuri, Paul R Walker
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27969473/ps01-05-early-and-persistent-oligoclonal-t-cell-expansion-correlates-with-durable-response-to-anti-pd1-therapy-in-nsclc-topic-medical-oncology
#17
Sope Olugbile, Kazuma Kiyotani, Jae-Hyun Park, Philip Hoffman, Livia Szeto, Jyoti Patel, Everett Vokes, Yusuke Nakamura
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27951441/resistance-to-pd1-pdl1-checkpoint-inhibition
#18
REVIEW
Jake S O'Donnell, Georgina V Long, Richard A Scolyer, Michele W L Teng, Mark J Smyth
For the first time in decades, patients with difficult-to-treat cancers such as advanced stage metastatic melanoma are being offered a glimpse of hope in the form of immunotherapies. By targeting factors that foster the development and maintenance of an immunosuppressive microenvironment within tumors, these therapies release the brakes on the host's own immune system; allowing cure of disease. Indeed, phase III clinical trials have revealed that therapies such as ipilimumab and pembrolizumab which target the CTLA4 and PD-1 immune checkpoints, respectively, have raised the three-year survival of patients with melanoma to ∼70%, and overall survival (>5years) to ∼30%...
January 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27942391/metastatic-basal-cell-carcinoma-with-amplification-of-pd-l1-exceptional-response-to-anti-pd1-therapy
#19
Sadakatsu Ikeda, Aaron M Goodman, Philip R Cohen, Taylor J Jensen, Christopher K Ellison, Garrett Frampton, Vincent Miller, Sandip P Patel, Razelle Kurzrock
Metastatic basal cell carcinomas are rare malignancies harbouring Hedgehog pathway alterations targetable by SMO antagonists (vismodegib/sonidegib). We describe, for the first time, the molecular genetics and response of a patient with Hedgehog inhibitor-resistant metastatic basal cell carcinoma who achieved rapid tumour regression (ongoing near complete remission at 4 months) with nivolumab (anti-PD1 antibody). He had multiple hallmarks of anti-PD1 responsiveness including high mutational burden (> 50 mutations per megabase; 19 functional alterations in tissue next-generation sequencing (NGS; 315 genes)) as well as PDL1/PDL2/JAK2 amplification (as determined by both tissue NGS and by analysis of plasma-derived cell-free DNA)...
2016: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/27940380/biomimetic-biodegradable-artificial-antigen-presenting-cells-synergize-with-pd-1-blockade-to-treat-melanoma
#20
A K Kosmides, R A Meyer, J W Hickey, K Aje, K N Cheung, J J Green, J P Schneck
Biomimetic materials that target the immune system and generate an anti-tumor responses hold promise in augmenting cancer immunotherapy. These synthetic materials can be engineered and optimized for their biodegradability, physical parameters such as shape and size, and controlled release of immune-modulators. As these new platforms enter the playing field, it is imperative to understand their interaction with existing immunotherapies since single-targeted approaches have limited efficacy. Here, we investigate the synergy between a PLGA-based artificial antigen presenting cell (aAPC) and a checkpoint blockade molecule, anti-PD1 monoclonal antibody (mAb)...
February 2017: Biomaterials
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