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https://www.readbyqxmd.com/read/28054442/markers-and-function-of-human-nk-cells-in-normal-and-pathological-conditions
#1
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/28038471/prognostic-impact-of-immune-microenvironment-in-laryngeal-and-pharyngeal-squamous-cell-carcinoma-immune-cell-subtypes-immuno-suppressive-pathways-and-clinicopathologic-characteristics
#2
Georgia Karpathiou, Francois Casteillo, Jean-Baptiste Giroult, Fabien Forest, Pierre Fournel, Alessandra Monaya, Marios Froudarakis, Jean Marc Dumollard, Jean Michel Prades, Michel Peoc'h
BACKGROUND: Immune system affects prognosis of various malignancies. Anti-immune pathways like PD-L1 and CTLA4 are used by the tumor to overcome immune system and they serve as immunotherapy targets. The immune microenvironment of head-and-neck squamous cell carcinoma (SCCHN) has not been sufficiently studied. PATIENTS AND METHODS: 152 SCCHN were immunohistochemically studied for the expression of CD3, CD8, CD57, CD4, granzyme b, CD20, CD163, S100, PD-L1, CTLA4 and CXCR4...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27997006/-nivolumab-in-second-line-treatment-of-squamous-non-small-cell-lung-cancer
#3
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/27966264/pd1-and-pdl1-expression-in-primary-central-nervous-system-diffuse-large-b-cell-lymphoma-are-frequent-and-expression-of-pd1-predicts-poor-survival
#4
Marion Four, Valère Cacheux, Ariane Tempier, Dolorès Platero, Michel Fabbro, Grégory Marin, Nicolas Leventoux, Valérie Rigau, Valérie Costes-Martineau, Vanessa Szablewski
Primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare and aggressive type of diffuse large B-cell lymphoma (DLBCL) whit poorly understood pathogenesis. Finding biomarkers associated with patient survival may be important for understanding its physiopathology and to develop new therapeutic approaches. We investigated 32 PCNS-DLBCL from immunocompetent patients for BCL2, CMYC, LMO2, and P53 expression and for cytogenetic aberrations of BCL2, BCL6, and MYC genes, all known for their prognostic value in systemic DLBCL (s-DLBCL)...
December 13, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27951441/resistance-to-pd1-pdl1-checkpoint-inhibition
#5
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
#6
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/27935862/targeting-of-interleukin-il-17a-inhibits-pdl1-expression-in-tumor-cells-and-induces-anticancer-immunity-in-an-estrogen-receptor-negative-murine-model-of-breast-cancer
#7
Yun-Feng Ma, Chen Chen, Dongqing Li, Min Liu, Zhuang-Wei Lv, Yanhong Ji, Jiru Xu
The expression of IL-17A and programmed death ligand 1 (PDL1) is increased in estrogen receptor-negative breast cancer. IL-17A promotes tumor cell survival and invasiveness and inhibits the antitumor immune response. The PDL1-PD1 (programmed death protein 1) signaling pathway promotes escape from immune surveillance in tumor cells. The pro-tumor properties of IL-17A and PDL1 in various cancers have been previously examined; however, the relationship and roles of IL-17A and PDL1 in ER-negative breast cancer have not been evaluated...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27920662/possible-noninvasive-biomarker-of-eosinophilic-esophagitis-clinical-and-experimental-evidence
#8
Sathisha Upparahalli Venkateshaiah, Murli Manohar, Alok K Verma, Uwe Blecker, Anil Mishra
Eosinophilic esophagitis (EoE) diagnosis and follow-up response to therapy is based on repeated endoscopies and histological examination for eosinophils/HPF. The procedure is invasive and risky in particular for the pediatric population. Presently, there is no highly sensitive and specific noninvasive blood test available to monitor the disease pathogenesis. Reports indicate the expression of PDL1 (CD274) on the eosinophils in allergic patients. Herein, we report that CD274-expressing and -nonexpressing eosinophils were detected in both examined pediatric and adult EoE patients...
September 2016: Case Reports in Gastroenterology
https://www.readbyqxmd.com/read/27912061/tumor-interferon-signaling-regulates-a-multigenic-resistance-program-to-immune-checkpoint-blockade
#9
Joseph L Benci, Bihui Xu, Yu Qiu, Tony J Wu, Hannah Dada, Christina Twyman-Saint Victor, Lisa Cucolo, David S M Lee, Kristen E Pauken, Alexander C Huang, Tara C Gangadhar, Ravi K Amaravadi, Lynn M Schuchter, Michael D Feldman, Hemant Ishwaran, Robert H Vonderheide, Amit Maity, E John Wherry, Andy J Minn
Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27900363/integration-of-genomics-and-histology-revises-diagnosis-and-enables-effective-therapy-of-refractory-cancer-of-unknown-primary-with-pdl1-amplification
#10
Stefan Gröschel, Martin Bommer, Barbara Hutter, Jan Budczies, David Bonekamp, Christoph Heining, Peter Horak, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Christina Geörg, Daniela Richter, Nicole Pfarr, Katrin Pfütze, Stephan Wolf, Peter Schirmacher, Dirk Jäger, Christof von Kalle, Benedikt Brors, Hanno Glimm, Wilko Weichert, Albrecht Stenzinger, Stefan Fröhling
Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision-making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multiagent chemotherapy...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27895920/pd1-pd-l1-inhibition-as-a-potential-radiosensitizer-in-head-and-neck-squamous-cell-carcinoma-a-case-report
#11
Misako Nagasaka, Mark Zaki, Harold Kim, S Naweed Raza, George Yoo, Ho-Sheng Lin, Ammar Sukari
BACKGROUND: Immunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint inhibitors and anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently investigated. CASE PRESENTATION: We report a case of locally relapsed non-resectable oral cavity squamous cell carcinoma, with excellent local control after pembrolizumab (MK3475) followed by radiotherapy...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27886124/advances-in-cancer-immunotherapy-in-solid-tumors
#12
REVIEW
Smitha Menon, Sarah Shin, Grace Dy
Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses...
November 24, 2016: Cancers
https://www.readbyqxmd.com/read/27854242/the-future-prospects-of-immune-therapy-in-gastric-and-esophageal-adenocarcinoma
#13
REVIEW
Walid L Shaib, Jean Paul A Nammour, Harpaul Gill, Mayur Mody, Nabil F Saba
The prognosis of esophageal cancers is poor and novel approaches are urgently needed. Despite improvements in outcomes with transtuzumab and ramucirumab, these improvements added an average of only 2 to 3 months with a median overall survival reported to be around 1 year. Comprehensive genomic sequencing has defined some molecular alterations with potential targets, but the majority of patients still do not benefit from druggable targets. Breakthroughs in immune checkpoint blockade have provided new therapeutic options in many cancers...
November 14, 2016: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/27827885/is-there-still-room-for-cancer-vaccines-at-the-era-of-checkpoint-inhibitors
#14
REVIEW
Soumaya Karaki, Marie Anson, Thi Tran, Delphine Giusti, Charlotte Blanc, Stephane Oudard, Eric Tartour
Checkpoint inhibitor (CPI) blockade is considered to be a revolution in cancer therapy, although most patients (70%-80%) remain resistant to this therapy. It has been hypothesized that only tumors with high mutation rates generate a natural antitumor T cell response, which could be revigorated by this therapy. In patients with no pre-existing antitumor T cells, a vaccine-induced T cell response is a rational option to counteract clinical resistance. This hypothesis has been validated in preclinical models using various cancer vaccines combined with inhibitory pathway blockade (PD-1-PDL1-2, CTLA-4-CD80-CD86)...
November 3, 2016: Vaccines
https://www.readbyqxmd.com/read/27821490/suppression-of-type-i-ifn-signaling-in-tumors-mediates-resistance-to-anti-pd-1-treatment-that-can-be-overcome-by-radiotherapy
#15
Xiaohong Wang, Jonathan E Schoenhals, Ailin Li, David R Valdecanas, Huiping Ye, Fenglin Zhang, Chad Tang, Ming Tang, Chang-Gong Liu, Xiuping Liu, Sunil Krishnan, James P Allison, Padmanee Sharma, Patrick Hwu, Ritsuko Komaki, Willem W Overwijk, Daniel R Gomez, Joe Y Chang, Stephen M Hahn, Maria Angelica Cortez, James W Welsh
Immune checkpoint therapies exhibit impressive efficacy in some patients with melanoma or lung cancer, but the lack of response in most cases presses the question of how general efficacy can be improved. In addressing this question, we generated a preclinical tumor model to study anti-PD-1 resistance by in vivo passaging of Kras-mutated, p53-deficient murine lung cancer cells (p53R172HΔg/+K-rasLA1/+) in a syngeneic host exposed to repetitive dosing with anti-mouse PD-1 antibodies. PDL1 (CD274) expression did not differ between the resistant and parental tumor cells...
November 7, 2016: Cancer Research
https://www.readbyqxmd.com/read/27819282/characterization-of-t-follicular-helper-cells-in-allogeneic-normal-pregnancy-and-pdl1-blockage-induced-abortion
#16
Weihong Zeng, Zhicui Liu, Siming Zhang, Jiabin Ren, Xiaoling Ma, Chuanmei Qin, Fuju Tian, Yan Zhang, Yi Lin
A deeper understanding of the immunological events during pregnancy will provide novel insights into the pathogenesis of pregnancy complications. The fundamental function of T follicular helper (Tfh) cells is to provide cognate help to B cells. Dysregulations of Tfh-cell function and/or development can result in various immunological diseases. However, the role and characteristics of Tfh cells during pregnancy remain unknown. Herein, an allogeneic-normal-pregnant mouse model was used, and we found that the CD4(+) T cells residing at the uterus and placenta (UP) displayed a Tfh-like phenotype; and the UP-derived CD4(+)CXCR5(hi)PD-1(hi) and CD4(+)CXCR5(hi)ICOS(hi) Tfh cells, which showed a memory/activation phenotype, reached their peak at mid-pregnancy...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27808592/pd1-and-pdl1-upregulation-and-survival-after-decitabine-treatment-in-lower-risk-mds
#17
Sameem Abedin, Leonidas C Platanias
No abstract text is available yet for this article.
November 3, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27802341/acute-malaria-induces-pd1-ctla4-effector-t-cells-with-cell-extrinsic-suppressor-function
#18
Maria Sophia Mackroth, Annemieke Abel, Christiane Steeg, Julian Schulze Zur Wiesch, Thomas Jacobs
In acute Plasmodium falciparum (P. falciparum) malaria, the pro- and anti-inflammatory immune pathways must be delicately balanced so that the parasitemia is controlled without inducing immunopathology. An important mechanism to fine-tune T cell responses in the periphery is the induction of coinhibitory receptors such as CTLA4 and PD1. However, their role in acute infections such as P. falciparum malaria remains poorly understood. To test whether coinhibitory receptors modulate CD4+ T cell functions in malaria, blood samples were obtained from patients with acute P...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27775076/multiplatform-based-molecular-subtypes-of-non-small-cell-lung-cancer
#19
F Chen, Y Zhang, E Parra, J Rodriguez, C Behrens, R Akbani, Y Lu, J M Kurie, D L Gibbons, G B Mills, I I Wistuba, C J Creighton
Non-small-cell lung cancer (NSCLC) demonstrates remarkable molecular diversity. With the completion of The Cancer Genome Atlas (TCGA), there is opportunity for systematic analyses of the entire TCGA NSCLC cohort, including comparisons and contrasts between different disease subsets. On the basis of multidimensional and comprehensive molecular characterization (including DNA methylation and copy, and RNA and protein expression), 1023 NSCLC cases-519 from TCGA adenocarcinoma (AD) project and 504 from TCGA squamous cell carcinoma (SQCC) project-were classified using a 'cluster-of-clusters' analytic approach...
October 24, 2016: Oncogene
https://www.readbyqxmd.com/read/27772919/pdl1-expression-in-triple-negative-breast-cancer-is-associated-with-tumour-infiltrating-lymphocytes-and-improved-outcome
#20
Rhiannon K Beckers, Christina Selinger, Ricardo Vilain, Jason Madore, James S Wilmott, Kate Harvey, Anne Holliday, Caroline L Cooper, Elizabeth Robbins, David Gillet, Catherine W Kennedy, Laurence Gluch, Hugh Carmalt, Cindy Mak, Sanjay Warrier, Harriet E Gee, Charles Chan, Anna McLean, Emily Walker, Catriona M McNeil, Jane M Beith, Alexander Swarbrick, Richard A Scolyer, Sandra A O'Toole
No abstract text is available yet for this article.
February 2016: Pathology
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