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https://www.readbyqxmd.com/read/28507806/preclinical-efficacy-of-immune-checkpoint-monotherapy-does-not-recapitulate-corresponding-biomarkers-based-clinical-predictions-in-glioblastoma
#1
Abhishek D Garg, Lien Vandenberk, Matthias Van Woensel, Jochen Belmans, Marco Schaaf, Louis Boon, Steven De Vleeschouwer, Patrizia Agostinis
Glioblastoma (GBM) is resistant to most multimodal therapies. Clinical success of immune-checkpoint inhibitors (ICIs) has spurred interest in applying ICIs targeting CTLA4, PD1 or IDO1 against GBM. This amplifies the need to ascertain GBM's intrinsic susceptibility (or resistance) toward these ICIs, through clinical biomarkers that may also "guide and prioritize" preclinical testing. Here, we interrogated the TCGA and/or REMBRANDT human patient-cohorts to predict GBM's predisposition toward ICIs. We exploited various broad clinical biomarkers, including mutational or predicted-neoantigen burden, pre-existing or basal levels of tumor-infiltrating T lymphocytes (TILs), differential expression of immune-checkpoints within the tumor and their correlation with particular TILs/Treg-associated functional signature and prognostic impact of differential immune-checkpoint expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28487385/immune-related-gene-expression-profiling-after-pd-1-blockade-in-non-small-cell-lung-carcinoma-head-and-neck-squamous-cell-carcinoma-and-melanoma
#2
Aleix Prat, Alejandro Navarro, Laia Paré, Noemí Reguart, Patricia Galvan, Tomás Pascual, Alex Martínez, Paolo Nuciforo, Laura Comerma, Llucia Alos, Nuria Pardo, Susana Cedrés, Cheng Fan, Joel S Parker, Lydia Gaba, Ivan Victoria, Nuria Viñolas, Ana Vivancos, Ana Arance, Enriqueta Felip
Antibody targeting of the immune checkpoint receptor PD1 produces therapeutic activity in a variety of solid tumors, but most patients exhibit partial or complete resistance to treatment for reasons that are unclear. In this study, we evaluated tumor speciments from 65 patients with melanoma, lung non-squamous, squamous cell lung or head and neck cancers who were treated with the approved PD1 targeting antibodies pembrolizumab or nivolumab. Tumor RNA before anti-PD1 therapy was analyzed on the nCounter system using the PanCancer 730-Immune Panel, and we identified 23 immune-related genes or signatures linked to response and progression-free survival (PFS)...
May 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28323504/pembrolizumab-use-for-the-treatment-of-advanced-melanoma
#3
Pol Specenier
Until recently, overall long term survival in patients with stage IV melanoma was lower than 10%. However, the treatment of melanoma has evolved rapidly over the last few years, with the advent of inhibitors of BRAF and MEK and of immunotherapeutic agents including ipilimumab, nivolumab, and pembrolizumab. Areas covered: This is a comprehensive review of the literature on the role of pembrolizumab in melanoma. Pembrolizumab is a Programmed Death Receptor 1 (PD-1) directed monoclonal antibody which is approved by FDA and EMA for the treatment of patients with metastatic melanoma...
June 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28217128/tumor-associated-lymphatic-vessels-upregulate-pdl1-to-inhibit-t-cell-activation
#4
Lothar C Dieterich, Kristian Ikenberg, Timur Cetintas, Kübra Kapaklikaya, Cornelia Hutmacher, Michael Detmar
Tumor-associated lymphatic vessels (LVs) play multiple roles during tumor progression, including promotion of metastasis and regulation of antitumor immune responses by delivering antigen from the tumor bed to draining lymph nodes (LNs). Under steady-state conditions, LN resident lymphatic endothelial cells (LECs) have been found to maintain peripheral tolerance by directly inhibiting autoreactive T-cells. Similarly, tumor-associated lymphatic endothelium has been suggested to reduce antitumor T-cell responses, but the mechanisms that mediate this effect have not been clarified...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28214182/opportunistic-autoimmunity-secondary-to-cancer-immunotherapy-oasi-an-emerging-challenge
#5
M Kostine, L Chiche, E Lazaro, P Halfon, C Charpin, D Arniaud, F Retornaz, P Blanco, N Jourde-Chiche, C Richez, C Stavris
With "checkpoint inhibitors" targeting PD1/PD-1-ligands or CTLA-4/CD28 pathways, immunotherapy has profoundly modified therapeutic strategies in oncology. First approved in refractory metastatic neoplasms (melanoma and lung adenocarcinoma), it is now being tested broadly in other cancers and/or as adjuvant treatment. For a significant proportion of patients, immunotherapy is responsible for "immunological" events, identified as Immune-Related Adverse Events (irAEs). Owing to the increasing number of prescriptions, identification and management of specific immunological side effects is crucial and requires close collaboration between oncologists and internists and/or other organ specialists...
February 14, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28197383/analysis-of-the-prognostic-role-of-an-immune-checkpoint-score-in-resected-non-small-cell-lung-cancer-patients
#6
Marta Usó, Eloísa Jantus-Lewintre, Silvia Calabuig-Fariñas, Ana Blasco, Eva García Del Olmo, Ricardo Guijarro, Miguel Martorell, Carlos Camps, Rafael Sirera
Tumors develop mechanisms to recruit tolerogenic immune cells and to induce the expression of molecules that act as immune checkpoints. This regulation of the immune microenvironment favors immune tolerance to the neoplastic cells. In this study, we have investigated the prognostic role of immune-checkpoint expression markers in a cohort of resectable non-small cell lung cancer (NSCLC) patients. RNA was isolated from fresh-frozen lung specimens (tumor and normal lung) (n = 178). RTqPCR was performed to analyze the relative expression of 20 immune-related genes that were normalized by the use of endogenous genes selected by GeNorm algorithm...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28162296/-efficacy-of-pd-1-pd-l1%C3%A2-immune-checkpoint-inhibitors-and-pd-l1%C3%A2-testing-in-thoracic-cancers
#7
Michaël Duruisseaux, Isabelle Rouquette, Julien Adam, Alexis Cortot, Aurélie Cazes, Laure Gibault, Diane Damotte, Sylvie Lantuejoul
Tumoral immune environment is a major component of cancer. Its composition and its organization represent a reproducible characteristic of tumors and a validated prognostic factor. In non-small cell lung cancer (NSCLC), cytotoxic T CD8+ lymphocyte density, associated with a Th1 environment and tertiary lymphoid structures impacts survival. Tumor cell-immune cell interaction is targeted by PD1/PD-L1 inhibitors. In advanced NSCLC, PD1/PD-L1 inhibitors are more effective than second-line chemotherapy. Pembrolizumab outperforms first-line chemotherapy in NSCLC strongly positive for PD-L1...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28145884/the-significance-of-programmed-cell-death-ligand-1-expression-in-resected-lung-adenocarcinoma
#8
Shafei Wu, Xiaohua Shi, Jian Sun, Yuanyuan Liu, Yufeng Luo, Zhiyong Liang, Jinghui Wang, Xuan Zeng
BACKGROUND: Lung adenocarcinoma (AD) is a common variant of non-small cell lung cancer (NSCLC). Programmed cell death protein 1/programmed cell death ligand 1 (PD1/PD-L1) are promising immunotherapy targets and its expression may be an important biomarker of predicting clinical response. In this study, we evaluated PD-L1 expression in conjunction with clinicopathological characteristics and outcomes in resected lung adenocarcinoma. RESULTS: This study included 133 cases of lung adenocarcinoma...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28137295/a-phase-ii-trial-of-stereotactic-body-radiotherapy-with-concurrent-anti-pd1-treatment-in-metastatic-melanoma-evaluation-of-clinical-and-immunologic-response
#9
Katrien De Wolf, Vibeke Kruse, Nora Sundahl, Mireille van Gele, Ines Chevolet, Reinhart Speeckaert, Lieve Brochez, Piet Ost
BACKGROUND: Antibodies blocking programmed cell death 1 (PD-1) have encouraging responses in patients with metastatic melanoma. Response to anti-PD-1 treatment requires pre-existing CD8+ T cells that are negatively regulated by PD-1-mediated adaptive immune resistance. Unfortunately, less than half of melanoma tumours have these characteristics. Combining anti-PD-1 treatment with other immunomodulating treatments to activate CD8+ T cells is therefore of vital importance to increase response rates and long-term survival benefit in melanoma patients...
January 31, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28033288/immune-checkpoint-proteins-pd-1-and-tim-3-are-both-highly-expressed-in-liver-tissues-and-correlate-with-their-gene-polymorphisms-in-patients-with-hbv-related-hepatocellular-carcinoma
#10
Zhu Li, Na Li, Fang Li, Zhihua Zhou, Jiao Sang, Yanping Chen, Qunying Han, Yi Lv, Zhengwen Liu
Immune checkpoint proteins programmed death-1 (PD-1) and T-cell immunoglobulin domain and mucin domain containing molecule-3 (TIM-3) expression and their gene polymorphisms have separately been shown to be associated with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study simultaneously examined PD-1 and TIM-3 expression in liver tissues and PD1 and TIM3 polymorphisms and analyzed their correlations in 171 patients with HBV-related HCC and 34 patients with HBV-related cirrhosis...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27997006/-nivolumab-in-second-line-treatment-of-squamous-non-small-cell-lung-cancer
#11
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
#12
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/27980047/practical-immuno-pet-radiotracer-design-considerations-for-human-immune-checkpoint-imaging
#13
Aaron T Mayer, Arutselvan Natarajan, Sydney R Gordon, Roy L Maute, Melissa N McCracken, Aaron M Ring, Irving L Weissman, Sanjiv S Gambhir
Immune checkpoint blockade has emerged as a promising cancer treatment paradigm. Unfortunately, there are still a large number of patients and malignancies that do not respond to therapy. A major barrier to validating biomarkers for the prediction and monitoring of responders to clinical checkpoint blockade has been the lack of imaging tools to accurately assess dynamic immune checkpoint expression. Here, we sought to optimize noninvasive immuno-PET imaging of human programmed death-ligand 1 (PD-L1) expression, in a preclinical model, using a small high-affinity engineered protein scaffold (HAC-PD1)...
April 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
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
#14
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/27912061/tumor-interferon-signaling-regulates-a-multigenic-resistance-program-to-immune-checkpoint-blockade
#15
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/27872087/tim-3-expression-on-tumor-infiltrating-pd-1-cd8-t-cells-correlates-with-poor-clinical-outcome-in-renal-cell-carcinoma
#16
Clémence Granier, Charles Dariane, Pierre Combe, Virginie Verkarre, Saïk Urien, Cécile Badoual, Hélène Roussel, Marion Mandavit, Patrice Ravel, Mathilde Sibony, Lucie Biard, Camélia Radulescu, Emeline Vinatier, Nadine Benhamouda, Michael Peyromaure, Stéphane Oudard, Arnaud Méjean, Marc-Olivier Timsit, Alain Gey, Eric Tartour
Inhibitory receptors expressed by T cells mediate tolerance to tumor antigens, with coexpression of these receptors exacerbating this dysfunctional state. Using the VectraR automated multiparametric immunofluorescence technique, we quantified intratumoral CD8(+) T cells coexpressing the inhibitory receptors PD-1 and Tim-3 from patients with renal cell carcinoma (RCC). A second validation cohort measured the same parameters by cytometry. The percentage of tumor-infiltrating CD8(+) T cells coexpressing PD-1 and Tim-3 correlated with an aggressive phenotype and a larger tumor size at diagnosis...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/27785054/prognostic-value-of-pd-l1-and-pd-1-expression-in-pulmonary-neuroendocrine-tumors
#17
Yangwei Fan, Ke Ma, Chuying Wang, Jing Ning, Yuan Hu, Danfeng Dong, Xuyuan Dong, Qianqian Geng, Enxiao Li, Yinying Wu
PURPOSE: Programmed death 1 (PD-1) receptor and its ligand, programmed death ligand-1 (PD-L1), play critical roles in the immune invasion of various tumors. This study aimed to explore the clinical significance of PD-L1/PD-1 expression in the progression of pulmonary neuroendocrine tumors (PNETs). METHODS: The expression of PD-L1 and PD-1 in 80 patients diagnosed with PNETs were investigated. Immunohistochemical analysis was performed on 80 formalin-fixed paraffin-embedded tissue specimens from PNETs and 20 corresponding cancer-adjacent tissue specimens...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27692305/the-combined-role-of-biomarkers-and-interim-pet-scan-in-prediction-of-treatment-outcome-in-classical-hodgkin-s-lymphoma-a-retrospective-european-multicentre-cohort-study
#18
Claudio Agostinelli, Andrea Gallamini, Luisa Stracqualursi, Patrizia Agati, Claudio Tripodo, Fabio Fuligni, Maria Teresa Sista, Stefano Fanti, Alberto Biggi, Umberto Vitolo, Luigi Rigacci, Francesco Merli, Caterina Patti, Alessandra Romano, Alessandro Levis, Livio Trentin, Caterina Stelitano, Anna Borra, Pier Paolo Piccaluga, Stephen Hamilton-Dutoit, Peter Kamper, Jan Maciej Zaucha, Bogdan Małkowski, Waldemar Kulikowski, Joanna Tajer, Edyta Subocz, Justyna Rybka, Christian Steidl, Alessandro Broccoli, Lisa Argnani, Randy D Gascoyne, Francesco d'Amore, Pier Luigi Zinzani, Stefano A Pileri
BACKGROUND: Early-interim fluorodeoxyglucose (FDG)-PET scan after two ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy courses (PET-2) represents the most effective predictor of treatment outcome in classical Hodgkin's lymphoma. We aimed to assess the predictive value of PET-2 combined with tissue biomarkers in neoplastic and microenvironmental cells for this disease. METHODS: We enrolled 208 patients with classical Hodgkin's lymphoma and treated with ABVD (training set), from Jan 1, 2002, to Dec 31, 2009, and validated the results in a fully matched independent cohort of 102 patients with classical Hodgkin's lymphoma (validation set), enrolled from Jan 1, 2008, to Dec 31, 2012...
October 2016: Lancet Haematology
https://www.readbyqxmd.com/read/27676581/p2-47-also-presented-as-pd1-02-the-role%C3%A2-of%C3%A2-pd-l1-expression-as-a-predictive-biomarker-in-advanced-nsclc-an-update-of-a-network-meta-analysis-track-immunotherapy
#19
Pedro Aguiar, Gilberto Lopes, Ilka Santoro, Hakaru Tadokoro, Carmelia Barreto, Ramon De Mello
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27676477/pd1-02-also-presented-as-p2-47-the-role-of-pd-l1-expression-as-a-predictive-biomarker-in-advanced-nsclc-an-update-of-a-network-meta-analysis
#20
Pedro Aguiar, Gilberto Lopes, Ilka Santoro, Hakaru Tadokoro, Carmelia Barreto, Ramon De Mello
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
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