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https://www.readbyqxmd.com/read/28096186/translation-reprogramming-is-an-evolutionarily-conserved-driver-of-phenotypic-plasticity-and-therapeutic-resistance-in-melanoma
#1
Paola Falletta, Luis Sanchez-Del-Campo, Jagat Chauhan, Maike Effern, Amy Kenyon, Christopher J Kershaw, Robert Siddaway, Richard Lisle, Rasmus Freter, Matthew J Daniels, Xin Lu, Thomas Tüting, Mark Middleton, Francesca M Buffa, Anne E Willis, Graham Pavitt, Ze'ev A Ronai, Tatjana Sauka-Spengler, Michael Hölzel, Colin R Goding
The intratumor microenvironment generates phenotypically distinct but interconvertible malignant cell subpopulations that fuel metastatic spread and therapeutic resistance. Whether different microenvironmental cues impose invasive or therapy-resistant phenotypes via a common mechanism is unknown. In melanoma, low expression of the lineage survival oncogene microphthalmia-associated transcription factor (MITF) correlates with invasion, senescence, and drug resistance. However, how MITF is suppressed in vivo and how MITF-low cells in tumors escape senescence are poorly understood...
January 17, 2017: Genes & Development
https://www.readbyqxmd.com/read/28094061/vitiligo-like-lesions-occurring-in-patients-receiving-anti-programmed-cell-death-1-therapies-are-clinically-and-biologically-distinct-from-vitiligo
#2
Maiana Larsabal, Aurélie Marti, Clément Jacquemin, Jérôme Rambert, Denis Thiolat, Léa Dousset, Alain Taieb, Caroline Dutriaux, Sorilla Prey, Katia Boniface, Julien Seneschal
BACKGROUND: The use of anti-programmed cell death (PD)-1 therapies in metastatic tumors is associated with cutaneous side effects including vitiligo-like lesions. OBJECTIVE: We sought to characterize clinically and biologically vitiligo-like lesions occurring in patients receiving anti-PD-1 therapies by studying a case series of 8 patients with metastatic tumors and 30 control subjects with vitiligo. METHODS: Eight patients receiving anti-PD-1 therapies with features of vitiligo-like lesions seen in our department were recruited...
January 13, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28093480/comprehensive-screening-for-pd-l1-expression-in-thyroid-cancer
#3
Soomin Ahn, Tae Hyuk Kim, Sun Wook Kim, Chang Seok Ki, Hye Won Jang, Jee Soo Kim, Jung Han Kim, Jun-Ho Choe, Jung Hee Shin, Soo Yeon Hahn, Young Lyun Oh, Jae Hoon Chung
PD-L1 expression is being considered a potential biomarker for response of anti-PD-1 or anti-PD-L1 agents in various tumors. The reported frequency of PD-L1 positivity varies in thyroid carcinomas, and multiple factors may contribute to the variability in PD-L1 positivity. We evaluated the PD-L1 expression in various thyroid cancers on a large scale. A total of 407 primary thyroid cancers with a median 13.7-year of follow-up were included. We evaluated the frequency of PD-L1 expression using a rabbit monoclonal antibody (clone SP142)...
February 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28089420/regression-of-intracranial-meningioma-following-treatment-with-nivolumab-case-report-and-review-of-the-literature
#4
Efrat Gelerstein, Assaf Berger, Tali Jonas-Kimchi, Ido Strauss, Andrew A Kanner, Deborah T Blumenthal, Maya Gottfried, Nevo Margalit, Zvi Ram, Tal Shahar
The treatment of refractory meningiomas remains a challenge for both neurosurgeons and neuro-oncologists. There have been no clinical reports of the use or effects of anti-PD-1 therapy in patients with meningioma. We describe a patient whose intracranial meningioma decreased significantly in size after treatment with nivolumab, a monoclonal antibody targeting PD-1, for a concomitant advanced lung cancer. This is the first clinical report suggesting that antibodies targeting PD-1 are effective in treating meningioma...
January 12, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28073845/agreement-between-programmed-cell-death-ligand-1-diagnostic-assays-across-multiple-protein-expression-cut-offs-in-non-small-cell-lung-cancer
#5
Marianne J Ratcliffe, Alan Sharpe, Anita Midha, Craig Barker, Marietta Scott, Paul Scorer, Hytham Al-Masri, Marlon Rebelatto, Jill Walker
PURPOSE: agents:Immunotherapies targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) demonstrate encouraging antitumor activity and manageable tolerability in non-small cell lung cancer (NSCLC), especially in patients with high tumor PD-L1 expression, as detected by companion or complementary diagnostic assays developed for individual agents. A laboratory is unlikely to use multiple assay platforms. Furthermore, commercially available diagnostic assays are not standardized and different assay methods could lead to inappropriate treatment selection...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28073785/safety-and-efficacy-of-allogeneic-hematopoietic-stem-cell-transplant-after-pd-1-blockade-in-relapsed-refractory-lymphoma
#6
Reid W Merryman, Haesook T Kim, Pier Luigi Zinzani, Carmelo Carlo-Stella, Stephen M Ansell, Miguel-Angel Perales, Abraham Avigdor, Ahmad S Halwani, Roch Houot, Tony Marchand, Nathalie Dhedin, Willy Lescaut, Anne Thiebaut-Bertrand, Sylvie François, Aspasia Stamatoullas-Bastard, Pierre-Simon Rohrlich, Hélène Labussière Wallet, Luca Castagna, Armando Santoro, Veronika Bachanova, Scott C Bresler, Amitabh Srivastava, Harim Kim, Emily Pesek, Marie Chammas, Carol Reynolds, Vincent T Ho, Joseph H Antin, Jerome Ritz, Robert J Soiffer, Philippe Armand
Anti-PD-1 monoclonal antibodies are being increasingly tested in patients with advanced lymphoma. Following treatment, many of those patients are likely to be candidates for allogeneic hematopoietic stem cell transplant (HSCT). However, the safety and efficacy of HSCT may be affected by prior PD-1 blockade. We conducted an international retrospective analysis of 39 patients with lymphoma who received prior treatment with a PD-1 inhibitor, at a median time of 62 days (7-260) before HSCT. After a median follow-up of 12 months, the one-year cumulative incidences of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD) were 44% and 23% respectively, while the one-year incidence of chronic GVHD was 41%...
January 10, 2017: Blood
https://www.readbyqxmd.com/read/28073132/hypothyroidism-in-cancer-patients-on-immune-checkpoint-inhibitors-with-anti-pd1-agents-insights-on-underlying-mechanisms
#7
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/28072716/pneumonitis-in-cancer-patients-receiving-anti-pd-1-and-radiotherapies-three-case-reports
#8
Chieh-Sheng Lu, Jin-Hwang Liu
INTRODUCTION: In development of novel therapies for the treatment of patient with cancer, the use of radiotherapy (RT) can produce significant local control and, in recent studies, has also been shown to mediate anti-tumor responses at distant sites by triggering and enhancing the endogenous cellular immune responses. Although RT induces an abscopal effect in some patients due to enhanced immune response to the tumor, immune-escape mechanisms, including up-regulation of programmed death-ligand 1 (PD-L1) on tumor cells, limit this benefit in other patients...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28063623/immune-checkpoint-inhibitors-in-lung-cancer-an-unheralded-opportunity
#9
R Marshall, A Popple, T Kordbacheh, J Honeychurch, C Faivre-Finn, T Illidge
Lung cancer remains the leading cause of cancer-related death worldwide, with non-small cell lung cancer accounting for 85% of the disease. Over 70% of patients present with locally advanced, non-resectable or metastatic disease and despite improvements in chemoradiotherapy regimens and the development of molecularly targeted agents, 5 year survival rates remain poor, with acquired resistance to novel targeted therapies becoming a growing concern. Currently there remains an unmet need in effectively treating and inducing durable responses in advanced disease...
January 4, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28062513/metastatic-melanoma-patient-had-complete-response-with-clonal-expansion-after-whole-brain-radiation-and-pd-1-blockade
#10
Cara L Haymaker, DaeWon Kim, Marc Uemura, Luis M Vence, Ann Phillip, Natalie McQuail, Paul D Brown, Irina Fernandez, Courtney W Hudgens, Caitlin Creasy, Wen-Jen Hwu, Padmanee Sharma, Michael T Tetzlaff, James P Allison, Patrick Hwu, Chantale Bernatchez, Adi Diab
We report here on a patient with metastatic melanoma who had extensive brain metastases. After being treated with the sequential combination of whole brain radiation therapy (WBRT) followed by the PD-1 inhibitory antibody, pembrolizumab, the patient had a durable complete response. Retrospective laboratory studies of T cells revealed that, after treatment with anti-PD-1 commenced, effector CD8(+) T cells in the blood expanded and the ratio of CD8(+):Treg T cells increased. A CD8(+) T-cell clone present in the initial brain metastases was expanded in the blood after anti-PD-1 treatment, which suggested an antitumor role for this clone...
January 6, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28059093/expression-of-pd-l1-and-presence-of-cd8-positive-t-cells-in-pre-treatment-specimens-of-locally-advanced-cervical-cancer
#11
Emeka K Enwere, Elizabeth N Kornaga, Michelle Dean, Theodora A Koulis, Tien Phan, Maria Kalantarian, Martin Köbel, Prafull Ghatage, Anthony M Magliocco, Susan P Lees-Miller, Corinne M Doll
Several of the cancer immunotherapies under investigation or in clinical use target the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling axis. PD-L1 expression in tumor samples has been used as a predictive marker for response to these therapeutics, and may also have independent prognostic utility when assessed along with immune cell markers. Our objectives were to assess the expression of PD-L1 in tumor specimens from a uniformly treated patient cohort with locally advanced cervical cancer, and to determine its prognostic significance along with the density of tumor-infiltrating T cells...
January 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28057180/utilisation-des-inhibiteurs-de-pd-1-dans-les-h%C3%A3-mopathies-lympho%C3%A3-des
#12
Laura Bounaix, Mohammed Bendouda, Jacques-Olivier Bay, Richard Lemal
ANTI-PD-1 ANTIBODIES THERAPEUTIC USE IN LYMPHOID NEOPLASMS: Immune checkpoints blockade is under investigation in oncology, and has demonstrated its clinical efficacy. In hematology, immune checkpoints blockade is in earlier stages of development, but there are strong evidences of PD-1 blockade anti-tumor efficacy in some lymphoid malignancies. In this review, we will discuss the main clinical results of PD-1 inhibitors in lymphoid neoplasms and the main perspectives of development.
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28057179/biomarqueurs-pr%C3%A3-dictifs-de-r%C3%A3-ponse-aux-traitements-bloquant-les-voies-de-costimulation-inhibitrices
#13
Franck Pagès, Clémence Granier, Amos Kirilovsky, Carine Elsissy, Eric Tartour
Immunotherapies targeting co-inhibitory receptors recently open a new promising approach of cancer treatment. Indeed, an objective clinical response was observed after treatment by anti-CTLA-4 and anti-PD-1 in many indications but the treatment still failed in 70 to 80 % of cases treated. Given the adverse effects and the high cost of these therapies, there is a need for the development of biomarkers. This review focus on potential predictive biomarkers. In peripheral blood, high level of Il-2 soluble receptor at baseline and absence of ICOS+ CD4-T lymphocytes induction may be associated with the absence of clinical response for melanoma patients treated by ipilimumab (anti-CTLA-4)...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28057178/immunoth%C3%A3-rapie-dans-les-cancers-de-la-prostate
#14
Stéphane Oudard, Constance Thibault, Antoine Angelergues, Eric Tartour, Marc Olivier Timsit, Arnaud Mejean, Constance Michel, Yann Vano
Immunotherapy is moving forward in prostate cancer. The autologous vaccine, Sipuleucel-T has been the first vaccine to be approved by FDA. First results with GVAX, tasquinimob or anti-PD-1 have been disappointing. Ipilimumab seen to be more active at an earlier stage of prostate disease. Identifying predictive factor or surrogate markers of activity of immunotherapy and which agents are clinically effective alone or in combination with others therapies such as hormonal or bone targeted therapies are warranted...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28057176/immunoth%C3%A3-rapie-et-m%C3%A3-lanome-l%C3%A2-exemple-des-anticorps-immunomodulateurs
#15
Cécile Pagès, Barouyr Baroudjian, Celeste Lebbé
Recently, metastatic melanoma has known real therapeutic improvement. Since 2011, 8 drugs have been approved for advanced melanoma such as immunotherapy checkpoint inhibitors. Chemotherapy is no longer used in the first setting of metastatic melanoma treatment. In 2010, the advent of ipilimumab, an anti CTLA 4 inhibitor, changed the scenario and in the following years, many studies confirmed the efficacy of nivolumab and pembrolizumab, two anti PD 1 inhibitors, as a first line treatment. Furthermore, the combination of first-line nivolumab plus ipilimumab might lead to improved outcomes compared with first-line ipilimumab alone in patients with advanced melanoma...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28055269/targeting-pd-1-pathway-a-new-hope-for-gastrointestinal-cancers
#16
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/28052254/pan-cancer-immunogenomic-analyses-reveal-genotype-immunophenotype-relationships-and-predictors-of-response-to-checkpoint-blockade
#17
Pornpimol Charoentong, Francesca Finotello, Mihaela Angelova, Clemens Mayer, Mirjana Efremova, Dietmar Rieder, Hubert Hackl, Zlatko Trajanoski
The Cancer Genome Atlas revealed the genomic landscapes of human cancers. In parallel, immunotherapy is transforming the treatment of advanced cancers. Unfortunately, the majority of patients do not respond to immunotherapy, making the identification of predictive markers and the mechanisms of resistance an area of intense research. To increase our understanding of tumor-immune cell interactions, we characterized the intratumoral immune landscapes and the cancer antigenomes from 20 solid cancers and created The Cancer Immunome Atlas (https://tcia...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28050779/a-current-perspective-on-cancer-immune-therapy-step-by-step-approach-to-constructing-the-magic-bullet
#18
REVIEW
Gabriele D'Errico, Heather L Machado, Bruno Sainz
Immunotherapy is the new trend in cancer treatment due to the selectivity, long lasting effects, and demonstrated improved overall survival and tolerance, when compared to patients treated with conventional chemotherapy. Despite these positive results, immunotherapy is still far from becoming the perfect magic bullet to fight cancer, largely due to the facts that immunotherapy is not effective in all patients nor in all cancer types. How and when will immunotherapy overcome these hurdles? In this review we take a step back to walk side by side with the pioneers of immunotherapy in order to understand what steps need to be taken today to make immunotherapy effective across all cancers...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28045749/histologic-assessment-of-lichenoid-dermatitis-observed-in-patients-with-advanced-malignancies-on-antiprogramed-cell-death-1-anti-pd-1-therapy-with-or-without-ipilimumab
#19
Shaun Chou, Shelley Ji Eun Hwang, Giuliana Carlos, Deepal Wakade, Pablo Fernandez-Penas
Lichenoid drug reaction is a common adverse reaction in patients taking immune-modulatory agents such as antiprogramed cell death (PD-1) and cytotoxic T lymphocyte antigen-4 agents. The authors describe the clinical and histologic features of lichenoid drug reaction in 20 biopsies from 15 patients on anti-PD-1 agents and 9 biopsies from 7 patients on anti-PD-1 plus ipilimumab therapy. Clinically, all except 2 patients presented with discrete, violaceous exanthematous papules to plaques. The lichenoid inflammation in the majority (18 of 29 biopsies) was florid although histology was quite heterogeneous...
January 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28039262/potential-predictive-value-of-tp53-and-kras-mutation-status-for-response-to-pd-1-blockade-immunotherapy-in-lung-adenocarcinoma
#20
Zhong-Yi Dong, Wenzhao Zhong, Xu-Chao Zhang, Jian Su, Zhi Xie, Si-Yang Liu, Hai-Yan Tu, Hua-Jun Chen, Yue-Li Sun, Qing Zhou, Jinji Yang, Xuening Yang, Jia-Xin Lin, Honghong Yan, Hao-Ran Zhai, Li-Xu Yan, Ri-Qiang Liao, Si-Pei Wu, Yi-Long Wu
PURPOSE: Although clinical studies have shown promise for targeting programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small cell lung cancer (NSCLC), the factors that predict which subtype patients will be responsive to checkpoint blockade are not fully understood. EXPERIMENTAL DESIGN: We performed an integrated analysis on the multiple-dimensional data types including genomic, transcriptomic, proteomic and clinical data from cohorts of lung adenocarcinoma public (Discovery Set) and internal (Validation Set) database and immunotherapeutic patients...
December 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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