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Cancer and immune checkpoint

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https://www.readbyqxmd.com/read/28433197/-what-is-the-place-of-the-combinations-for-immunotherapy-with-chemotherapy-or-with-other-immune-checkpoint-inhibitors
#1
REVIEW
Gaëlle Douchet, Sandrine Aspeslagh
Immune checkpoint blockade by the use of anti-PD(L)1 or anti-CTLA4 antibodies can induce long lasting disease response and maybe cure in a lot of advanced cancer patients. This ongoing immunotherapy revolution has given new hope to cancer patients and oncologists. However, still the majority of cancer patients do not respond to immune checkpoint blockade and novel therapeutical possibilities are being tested in several clinical trials. One of the possibilities to enhance responses to immune checkpoint blockade is the combination with chemotherapy or with other immune checkpoint blockade molecules...
April 19, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28431920/the-microbiome-in-anti-cancer-therapy
#2
REVIEW
Stavros Bashiardes, Timur Tuganbaev, Sara Federici, Eran Elinav
The commensal microbiome constitutes an important modulator of host physiology and risk of disease, including cancer development and progression. Lately, the microbiome has been suggested to modulate the efficacy of anti-cancer treatment. Examples include chemotherapy and total body irradiation-induced barrier function disruption, leading to microbial efflux that drives activation of anti-tumorigenic T cells; Microbiome-driven release of reactive oxygen species contributing to the efficacy of platinum salts; and microbiome-induced immune priming promoting the anti-tumor effects of alkylating chemotherapy and immune checkpoint inhibitors...
April 18, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28430133/nuclear-molecular-imaging-strategies-in-immune-checkpoint-inhibitor-therapy
#3
REVIEW
Kasper F Guldbrandsen, Helle W Hendel, Seppo W Langer, Barbara M Fischer
Immune checkpoint inhibitor therapy (ICT) is a new treatment strategy developed for the treatment of cancer. ICT inhibits pathways known to downregulate the innate immune response to cancer cells. These drugs have been shown to be effective in the treatment of a variety of cancers, including metastatic melanoma and lung cancer. Challenges in response evaluation of patients in ICT have risen as immune related side effects and immune cell infiltration may be confused with progressive disease. Furthermore, the timing of the evaluation scan may be challenged by relatively slow responses...
April 21, 2017: Diagnostics
https://www.readbyqxmd.com/read/28428947/update-on-programmed-death-1-and-programmed-death-ligand-1-inhibition-in-the-treatment-of-advanced-or-metastatic-non-small-cell-lung-cancer
#4
REVIEW
Marco A J Iafolla, Rosalyn A Juergens
PURPOSE: Non-small-cell lung cancer (NSCLC) has a large worldwide prevalence with a high mortality rate. Chemotherapy has offered modest improvements in survival over the past two decades. Immune checkpoint modulation with programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibition has shown the promise of changing the future landscape of cancer therapy. This update reviews recent advances in the treatment of NSCLC with immune checkpoint modulation. METHODS: Publications and proceedings were identified from searching PubMed and proceedings from the annual meetings of the American Society of Clinical Oncology, European Society for Medical Oncology, and European Lung Cancer Conference...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28428884/phase-i-clinical-trial-of-combination-imatinib-and-ipilimumab-in-patients-with-advanced-malignancies
#5
Matthew J Reilley, Ann Bailey, Vivek Subbiah, Filip Janku, Aung Naing, Gerald Falchook, Daniel Karp, Sarina Piha-Paul, Apostolia Tsimberidou, Siqing Fu, JoAnn Lim, Stacie Bean, Allison Bass, Sandra Montez, Luis Vence, Padmanee Sharma, James Allison, Funda Meric-Bernstam, David S Hong
BACKGROUND: Imatinib mesylate can induce rapid tumor regression, increase tumor antigen presentation, and inhibit tumor immunosuppressive mechanisms. CTLA-4 blockade and imatinib synergize in mouse models to reduce tumor volume via intratumoral accumulation of CD8+ T cells. We hypothesized that imatinib combined with ipilimumab would be tolerable and may synergize in patients with advanced cancer. METHODS: Primary objective of the dose-escalation study (3 + 3 design) was to establish the maximum tolerated dose (MTD) and recommended phase II dose...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428503/-cancer-immunotherapy-utilizing-t-cell-receptor-gene-engineering
#6
Hiroaki Ikeda
Immune-checkpoint inhibitors have shown their efficacy in the treatment of patients with many kinds of progressive/relapsed cancers. However, the efficacy remains as 10-40%of the patients in most type of cancers, suggesting that the development of new therapy for patients resistant to the therapy is an urgent unmet need. Adoptive therapy with tumor-specific T cells is a promising therapy that can be effective in patients who are not benefited from the immune-checkpoint inhibitors. The T cell therapy with genetic engineering in T cell receptor(TCR)is expected to be a universal therapy because this therapy can be applicable for patients with many kinds of cancers...
April 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28428277/immune-gene-expression-is-associated-with-genomic-aberrations-in-breast-cancer
#7
Anton Safonov, Tingting Jiang, Giampaolo Bianchini, Balázs Győrffy, Thomas Karn, Christos Hatzis, Lajos Pusztai
The presence of tumor-infiltrating lymphocytes (TIL) is a favorable prognostic factor in breast cancer, but what drives immune infiltration remains unknown. Here we examine if clonal heterogeneity, total mutation load, neoantigen load, copy number variations (CNV), gene- or pathway-level somatic mutations, or germline polymorphisms (SNP) are associated with immune metagene expression in breast cancer subtypes. Thirteen published immune metagenes correlated separately with genomic metrics in the 3 major breast cancer subtypes...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427523/combination-of-immune-checkpoint-inhibitors-and-radiotherapy-review-of-the-literature
#8
REVIEW
Alessandro Sindoni, Fabio Minutoli, Giorgio Ascenti, Stefano Pergolizzi
Literature experiences in cancer treatment usually deal with either targeting the tumour cell or the immune system, which often fail to reach the curative purposes in many solid tumours. On the other hand, one mechanism of radiation-induced tumour control is the activation of the adaptive immune system by tumour antigen release following radiotherapy. So, combining radiation therapy with immune checkpoint blockade treatment at the same time may represent a way to stimulate the adaptive immune system, with further amplification of immune responses reached through systemic immune checkpoint blockade...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427522/the-role-of-anti-pd-1-and-anti-pd-l1-agents-in-the-treatment-of-diffuse-large-b-cell-lymphoma-the-future-is-now
#9
REVIEW
Luis Miguel Juárez-Salcedo, Jose Sandoval-Sus, Lubomir Sokol, Julio C Chavez, Samir Dalia
Immune checkpoints inhibitors have been incorporated into standard treatment protocols for advanced solid tumors. The aim of T-cell-based immune therapy in cancer has been to generate durable clinical benefits for patients, paired with enhanced side effect profiles. The beneficial antitumoral activity of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has been thoroughly demonstrated in certain metastatic malignancies (e.g. melanoma, non-small cell lung cancer, renal cell carcinoma); however, the therapeutic role in lymphoid cancers is complex...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427513/polymerase-proofreading-domain-mutations-new-opportunities-for-immunotherapy-in-hypermutated-colorectal-cancer-beyond-mmr-deficiency
#10
REVIEW
Rémi Bourdais, Benoît Rousseau, Anaïs Pujals, Helene Boussion, Charlotte Joly, Aude Guillemin, Isabelle Baumgaertner, Cindy Neuzillet, Christophe Tournigand
Immune checkpoint inhibition is a new therapeutic strategy that has shown promising efficacy in many cancer types. Significant activity associated with mismatch repair (MMR) deficiency has been observed in hypermutated, microsatellite unstable (MSI) metastatic colorectal cancer (CRC). Beyond deficient-MMR tumors, somatic or germline DNA polymerase D1 (POLD1) or DNA polymerase E (POLE) alterations cause a hypermutated phenotype in CRC. This recently identified and rare subgroup of proficient-MMR tumors may also benefit from immunotherapy...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28425751/development-of-red-blood-cell-autoantibodies-following-treatment-with-checkpoint-inhibitors-a-new-class-of-anti-neoplastic-immunotherapeutic-agents-associated-with-immune-dysregulation
#11
Laura L Cooling, John Sherbeck, Jonathon C Mowers, Sheri L Hugan
Ipilimumab, nivolumab, and pembrolizumab represent a new class of immunotherapeutic drugs for treating patients with advanced cancer. Known as checkpoint inhibitors, these drugs act to upregulate the cellular and humoral immune response to tumor antigens by inhibiting T-cell autoregulation. As a consequence, they can be associated with immune-related adverse events (irAEs) due to loss of self-tolerance, including rare cases of immune-related cytopenias. We performed a retrospective clinical chart review, including serologic, hematology, and chemistry laboratory results, of two patients who developed red blood cell (RBC) autoantibodies during treatment with a checkpoint inhibitor...
January 2017: Immunohematology
https://www.readbyqxmd.com/read/28424759/antiangiogenesis-for-advanced-non-small-cell-lung-cancer-in-the-era-of-immunotherapy-and-personalized-medicine
#12
REVIEW
Samer Tabchi, Normand Blais
Over the past decade, patients with advanced non-small-cell lung cancer (NSCLC) have witnessed substantial advances in regards to therapeutic alternatives. Among newly developed agents, angiogenesis inhibitors were extensively tested in different settings and have produced some favorable outcomes despite several shortcomings. Bevacizumab is the most examined agent in this context and has demonstrated significant survival benefits when combined with standard chemotherapy in eligible patients. Preliminary results on the addition of bevacizumab to erlotinib in patients with EGFR-mutated NSCLC seem promising...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28424516/slamf7-is-critical-for-phagocytosis-of-haematopoietic-tumour-cells-via-mac-1-integrin
#13
Jun Chen, Ming-Chao Zhong, Huaijian Guo, Dominique Davidson, Sabrin Mishel, Yan Lu, Inmoo Rhee, Luis-Alberto Pérez-Quintero, Shaohua Zhang, Mario-Ernesto Cruz-Munoz, Ning Wu, Donald C Vinh, Meenal Sinha, Virginie Calderon, Clifford A Lowell, Jayne S Danska, André Veillette
Cancer cells elude anti-tumour immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors. Phagocytosis by macrophages plays a critical role in cancer control. Therapeutic blockade of signal regulatory protein (SIRP)-α, an inhibitory receptor on macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour cell elimination in vitro and in vivo, suggesting that blockade of the SIRPα-CD47 checkpoint could be useful in treating human cancer...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28423491/the-mir-25-93-106b-cluster-regulates-tumor-metastasis-and-immune-evasion-via-modulation-of-cxcl12-and-pd-l1
#14
Michele Cioffi, Sara M Trabulo, Mireia Vallespinos, Deepak Raj, Tony Bou Kheir, Meng-Lay Lin, Julfa Begum, Ann-Marie Baker, Ala Amgheib, Jaimy Saif, Manuel Perez, Joaquim Soriano, Manuel Desco, Maria Victoria Gomez-Gaviro, Lorena Cusso, Diego Megias, Alexandra Aicher, Christopher Heeschen
The stromal microenvironment controls response to injury and inflammation, and is also an important determinant of cancer cell behavior. However, our understanding of its modulation by miRNA (miR) and their respective targets is still sparse. Here, we identified the miR-25-93-106b cluster and two new target genes as critical drivers for metastasis and immune evasion of cancer cells. Using miR-25-93-106b knockout mice or antagomiRs, we demonstrated regulation of the production of the chemoattractant CXCL12 controlling bone marrow metastasis...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422766/an-immunoscore-using-pd-l1-cd68-and-tumor-infiltrating-lymphocytes-tils-to-predict-response-to-neoadjuvant-chemotherapy-in-invasive-breast-cancer
#15
Lauren E McLemore, Murali Janakiram, Joseph Albanese, Nella Shapiro, Yungtai Lo, Xingxing Zang, Susan Fineberg
Response to neoadjuvant chemotherapy (NAC) in invasive breast cancer (IBC) is partly regulated by the immune microenvironment. We evaluated immune checkpoint PD-L1 expression, presence of CD68+ cells of macrophage/monocytic lineage and stromal tumor-infiltrating lymphocytes (TILs) in prechemotherapy biopsies and correlated with NAC response. We studied 76 cases of IBC. Prechemotherapy biopsies with >30% TILs were considered lymphocyte-rich IBC. We performed immunohistochemistry for PD-L1 and CD68. Prechemotherapy cores showing >1% PD-L1+ immune or tumor cells were considered positive...
April 18, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28421272/-the-pathology-of-adverse-events-with-immune-checkpoint-inhibitors
#16
V H Koelzer, K Glatz, L Bubendorf, A Weber, A Gaspert, G Cathomas, A Lugli, A Zippelius, W Kempf, K D Mertz
BACKGROUND: Immunotherapy has gained importance with the development of new effective cancer treatments. Immune checkpoint inhibitors (ICI) are monoclonal antibodies that promote T‑cell mediated tumor immune rejection. Checkpoint blockade also carries the risk of inducing autoimmune reactions ("immune related adverse events", irAEs). The diagnosis and classification of irAEs constitute a new and important field in pathology. AIM: Practice-oriented review of the diagnosis and classification of irAEs...
April 18, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28420805/immunotherapeutic-approaches-for-hepatocellular-carcinoma
#17
Vito Longo, Antonio Gnoni, Andrea Casadei Gardini, Salvatore Pisconti, Antonella Licchetta, Mario Scartozzi, Riccardo Memeo, Vincenzo Ostilio Palmieri, Giuseppe Aprile, Daniele Santini, Patrizia Nardulli, Nicola Silvestris, Oronzo Brunetti
Hepatocellular carcinoma (HCC) is a cancer with a high mortality rate due to the fact that the diagnosis usually occurs at anadvanced stage. Even in case of curative surgical treatment, recurrence is common. Sorafenib and regorafenib are the only therapeutic agents that have been demonstrated to be effective in advanced HCC, thus novel curative approaches are urgently needed. Recent studies focus on the role of immune system in HCC. In fact, the unique immune response in the liver favors tolerance, which can represent a real challenge for conventional immunotherapy in these patients...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420659/very-low-expression-of-pd-l1-in-medullary-thyroid-carcinoma
#18
Massimo Bongiovanni, Caterina Rebecchini, Chiara Saglietti, Jean-Luc Bulliard, Laura Marino, Laurence De Leval, Gerasimos P Sykiotis
Monoclonal antibodies that inhibit the interaction between PD1 and PD-L1 are approved for clinical use in several cancer types, and they are also in clinical trials for additional indications, including thyroid carcinomas. A few papers have reported on PD-L1 expression in thyroid carcinomas, including a recent large study by Ahn et al. in Endocrine-Related Cancer using tissue microarrays on differentiated and anaplastic thyroid carcinoma. However, the expression of PD-L1 in medullary thyroid carcinoma (MTC) has not been reported so far, even though ongoing clinical studies aim to test the effectiveness of checkpoint inhibitors in this rare histotype as well...
April 18, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28420421/analysis-of-100-000-human-cancer-genomes-reveals-the-landscape-of-tumor-mutational-burden
#19
Zachary R Chalmers, Caitlin F Connelly, David Fabrizio, Laurie Gay, Siraj M Ali, Riley Ennis, Alexa Schrock, Brittany Campbell, Adam Shlien, Juliann Chmielecki, Franklin Huang, Yuting He, James Sun, Uri Tabori, Mark Kennedy, Daniel S Lieber, Steven Roels, Jared White, Geoffrey A Otto, Jeffrey S Ross, Levi Garraway, Vincent A Miller, Phillip J Stephens, Garrett M Frampton
BACKGROUND: High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors and has been shown to be more significantly associated with response to PD-1 and PD-L1 blockade immunotherapy than PD-1 or PD-L1 expression, as measured by immunohistochemistry (IHC). The distribution of TMB and the subset of patients with high TMB has not been well characterized in the majority of cancer types. METHODS: In this study, we compare TMB measured by a targeted comprehensive genomic profiling (CGP) assay to TMB measured by exome sequencing and simulate the expected variance in TMB when sequencing less than the whole exome...
April 19, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28419570/oral-lichenoid-reactions-associated-with-anti-pd-1-pd-l1-therapies-clinicopathological-findings
#20
V Sibaud, C Eid, V R Belum, P Combemale, B Barres, L Lamant, L Mourey, C Gomez-Roca, C L Estilo, R Motzer, E Vigarios, Mario E Lacouture
Immune checkpoint inhibitors targeting the programmed cell death receptor-1 (PD-1) or its ligand (PD-L1) show broad activity across different tumor types and currently represent one of the keystones of cancer management. Dermatologic toxicities are one of the most frequent immune-related adverse events (irAEs) induced by these new monoclonal antibodies. Maculopapular rash, pruritus, exacerbation of psoriasis or more specific autoimmune disorders (e.g. vitiligo, alopecia areata, and bullous pemphigoid) are amongst the most commonly reported AEs...
April 17, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
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