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https://www.readbyqxmd.com/read/29165283/decreased-survival-after-combining-thoracic-irradiation-and-an-anti-pd-1-antibody-correlated-with-increased-t-cell-infiltration-into-cardiac-and-lung-tissues
#1
Carey J Myers, Bo Lu
No abstract text is available yet for this article.
December 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29164593/immune-correlates-of-clinical-outcome-in-melanoma
#2
REVIEW
Graham Pawelec
Melanoma has long been recognized as a potentially immunogenic tumour, but only recently has it become clear that the reason for this resides in its many UV-induced mutations and expression of multiple autoantigens which can be targeted by the immune system. The first successful applications of immune-based treatments included passive immunotherapy using high-dose IL-2 and/or adoptive transfer of NK-cells, as well as active immunotherapy using whole cell-derived or peptide vaccines. In the intervening decades, it has become clear that these approaches can lead to durable responses in stage III/IV melanoma, and even to functional cures - but only in a vanishingly small fraction of patients...
November 21, 2017: Immunology
https://www.readbyqxmd.com/read/29164492/advanced-melanoma-current-treatment-options-biomarkers-and-future-perspectives
#3
REVIEW
Elisa A Rozeman, Tim J A Dekker, John B A G Haanen, Christian U Blank
Malignant melanoma accounts for the highest number of deaths from skin cancer, and the prognosis of patients with stage IV disease has historically been poor. Novel insights into both mutations driving tumorigenesis and immune escape mechanisms of these tumors have led to effective treatment options that have revolutionized the treatment of this disease. Targeting the MAPK kinase pathway (with BRAF and MEK inhibitors), as well as targeting checkpoints, such as cytotoxic T-lymphocyte associated protein 4 (CTLA-4) or programmed death 1 (PD-1), have improved overall survival in patients with late-stage melanoma, and biomarker research for personalized therapy is ongoing for each of these treatment modalities...
November 21, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/29163851/checkpoint-inhibitors-in-endometrial-cancer-preclinical-rationale-and-clinical-activity
#4
REVIEW
Gloria Mittica, Eleonora Ghisoni, Gaia Giannone, Massimo Aglietta, Sofia Genta, Giorgio Valabrega
Context: Treatment of advanced and recurrent endometrial cancer (EC) is still an unmet need for oncologists and gynecologic oncologists. The Cancer Genome Atlas Research Network (TCGA) recently provided a new genomic classification, dividing EC in four subgroups. Two types of EC, the polymerase epsilon (POLE)-ultra-mutated and the microsatellite instability-hyper-mutated (MSI-H), are characterized by a high mutation rate providing the rationale for a potential activity of checkpoint inhibitors...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163826/hdac-inhibitors-enhance-neratinib-activity-and-when-combined-enhance-the-actions-of-an-anti-pd-1-immunomodulatory-antibody-in-vivo
#5
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Paul Dent
Patients whose NSCLC tumors become afatinib resistant presently have few effective therapeutic options to extend their survival. Afatinib resistant NSCLC cells were sensitive to clinically relevant concentrations of the irreversible pan-HER inhibitor neratinib, but not by the first generation ERBB1/2/4 inhibitor lapatinib. In multiple afatinib resistant NSCLC clones, HDAC inhibitors reduced the expression of ERBB1/3/4, but activated c-SRC, which resulted in higher total levels of ERBB1/3 phosphorylation. Neratinib also rapidly reduced the expression of ERBB1/2/3/4, c-MET and of mutant K-/N-RAS; K-RAS co-localized with phosphorylated ATG13 and with cathepsin B in vesicles...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163822/structural-basis-of-the-therapeutic-anti-pd-l1-antibody-atezolizumab
#6
Fei Zhang, Xiaoqiang Qi, Xiaoxiao Wang, Diyang Wei, Jiawei Wu, Lingling Feng, Haiyan Cai, Yugang Wang, Naiyan Zeng, Ting Xu, Aiwu Zhou, Ying Zheng
Monoclonal antibodies targeting PD-1/PD-L1 signaling pathway have achieved unprecedented success in cancer treatment over the last few years. Atezolizumab is the first PD-L1 monoclonal antibody approved by US FDA for cancer therapy; however the molecular basis of atezolizumab in blocking PD-1/PD-L1 interaction is not fully understood. Here we have solved the crystal structure of PD-L1/atezolizumab complex at 2.9 angstrom resolution. The structure shows that atezolizumab binds the front beta-sheet of PD-L1 through three CDR loops from the heavy chain and one CDR loop from the light chain...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163789/prostaglandin-e2-and-pd-1-mediated-inhibition-of-antitumor-ctl-responses-in-the-human-tumor-microenvironment
#7
Jie Miao, Xu Lu, Yuefeng Hu, Chunmei Piao, Xuan Wu, Xuesong Liu, Caiting Huang, Yue Wang, Dan Li, Jingwei Liu
Accumulating evidence indicates that inflammation plays a critical role in cancer development; however, mechanisms of immunosuppression hinder productive anti-tumor immunity to limit immunopathology. Tumor-specific cytotoxic T lymphocyte (CTL) dysfunction or exhaustion by upregulating inhibitory receptors such as programmed cell death 1 (PD-1) in tumor-bearing hosts is one such mechanism. Identification and blockade of the pathways that induce CTL dysfunction has been shown to partially restore CTL function in tumor-bearing hosts...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163786/axl-inhibition-induces-the-antitumor-immune-response-which-can-be-further-potentiated-by-pd-1-blockade-in-the-mouse-cancer-models
#8
Zhiqiang Guo, Yan Li, Dandan Zhang, Jiaying Ma
Immune checkpoint blockers (ICB) have emerged as a promising new class of antitumor agents which significantly change the treatment landscape in a range of tumors; however, cancer patients benefited from ICB-based immunotherapy remains limited, scoring the need to explore the combination treatments with synergistic mechanisms of action. Axl receptor tyrosine kinase critically involves in the carcinogenesis of multiple cancers due to its dual roles in both promoting cancer invasion and metastasis and suppressing myeloid cell activation and function...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163783/abundant-expression-of-tim-3-lag-3-pd-1-and-pd-l1-as-immunotherapy-checkpoint-targets-in-effusions-of-mesothelioma-patients
#9
Elly Marcq, Jorrit De Waele, Jonas Van Audenaerde, Eva Lion, Eva Santermans, Niel Hens, Patrick Pauwels, Jan P van Meerbeeck, Evelien L J Smits
Malignant pleural mesothelioma (MPM) is an aggressive cancer with an increasing incidence, poor prognosis and limited effective treatment options. Hence, new treatment strategies are warranted which include immune checkpoint blockade approaches with encouraging preliminary data. Research on the immunological aspects of the easily accessible mesothelioma microenvironment could identify prognostic and/or predictive biomarkers and provide useful insights for developing effective immunotherapy. In this context, we investigated the immune cell composition of effusions (pleural and ascites fluids) from 11 different chemotherapy-treated MPM patients...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163509/downregulated-il-21-response-and-t-follicular-helper-cell-exhaustion-correlate-with-compromised-cd8-t-cell-immunity-during-chronic-toxoplasmosis
#10
Magali M Moretto, SuJin Hwang, Imtiaz A Khan
CD8 T cells are important for maintaining the chronicity of Toxoplasma gondii infection. In a T. gondii encephalitis susceptible model, we recently demonstrated that CD4 T cells play an essential helper role in the maintenance of the effector response and CD8 T cell dysfunctionality was linked to CD4 T cell exhaustion. However, CD4 T cells are constituted of different subsets with various functions and the population(s) providing help to the CD8 T cells has not yet been determined. In the present study, T follicular helper cells (Tfh), which are known to be essential for B cell maturation and are one of the main sources of IL-21, were significantly increased during chronic toxoplasmosis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163490/immune-checkpoint-molecules-on-tumor-infiltrating-lymphocytes-and-their-association-with-tertiary-lymphoid-structures-in-human-breast-cancer
#11
Cinzia Solinas, Soizic Garaud, Pushpamali De Silva, Anaïs Boisson, Gert Van den Eynden, Alexandre de Wind, Paolo Risso, Joel Rodrigues Vitória, François Richard, Edoardo Migliori, Grégory Noël, Hugues Duvillier, Ligia Craciun, Isabelle Veys, Ahmad Awada, Vincent Detours, Denis Larsimont, Martine Piccart-Gebhart, Karen Willard-Gallo
There is an exponentially growing interest in targeting immune checkpoint molecules in breast cancer (BC), particularly in the triple-negative subtype where unmet treatment needs remain. This study was designed to analyze the expression, localization, and prognostic role of PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM3 in primary BC. Gene expression analysis using the METABRIC microarray dataset found that all six immune checkpoint molecules are highly expressed in basal-like and HER2-enriched compared to the other BC molecular subtypes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163160/aberrant-wnt-beta-catenin-pathway-activation-in-dialysate-induced-peritoneal-fibrosis
#12
Yuanyuan Guo, Lin Sun, Li Xiao, Rong Gou, Yudong Fang, Yan Liang, Ruiqiang Wang, Ningjun Li, Fuyou Liu, Lin Tang
Peritoneal dialysis (PD)-associated peritoneal fibrosis is a chronic progress which induces ultrafiltration failure. It remains a challenge to prevent the progression of PD-associated fibrosis in clinic practice. Wnt/β-catenin pathway plays important role in many severe fibrotic diseases, here we investigated its contribution to the development of peritoneal damage. We isolated mesothelial cells (MC) from the effluent of PD patients and found that the expressions of Wnt1, Wnt5a, β-catenin, and LEF1 were increased in patients with more than 1-year PD compared with patients who just started with PD (<1 month)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29160310/cyclin-d-cdk4-kinase-destabilizes-pd-l1-via-cul3-spop-to-control-cancer-immune-surveillance
#13
Jinfang Zhang, Xia Bu, Haizhen Wang, Yasheng Zhu, Yan Geng, Naoe Taira Nihira, Yuyong Tan, Yanpeng Ci, Fei Wu, Xiangpeng Dai, Jianping Guo, Yu-Han Huang, Caoqi Fan, Shancheng Ren, Yinghao Sun, Gordon J Freeman, Piotr Sicinski, Wenyi Wei
Treatments that target immune checkpoints, such as the one mediated by programmed cell death protein 1 (PD-1) and its ligand PD-L1, have been approved for treating human cancers with durable clinical benefit(1,2). However, many cancer patients fail to respond to anti-PD-1/PD-L1 treatment, and the underlying mechanism(s) is not well understood(3-5). Recent studies revealed that response to PD-1/PD-L1 blockade might correlate with PD-L1 expression levels in tumor cells(6,7). Hence, it is important to mechanistically understand the pathways controlling PD-L1 protein expression and stability, which can offer a molecular basis to improve the clinical response rate and efficacy of PD-1/PD-L1 blockade in cancer patients...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29159009/myasthenia-gravis-induced-by-nivolumab-a-case-report
#14
Jeet J Mehta, Eamon Maloney, Sachin Srinivasan, Patrick Seitz, Michael Cannon
Nivolumab is a programmed cell death receptor (PD-1) inhibitor therapy for aggressive cancers; however, it poses a risk of immune-related adverse side effects. We present a 73-year-old male with renal cell carcinoma who developed myasthenia gravis (MG) after being treated with nivolumab, proven by acetylcholine receptor antibodies. Our patient presented with symptoms of fatigue and upper and lower extremity weakness, eventually resulting in respiratory failure as a result of MG. Nivolumab is an emerging therapy for advanced cancers but poses severe immune-related adverse events...
September 20, 2017: Curēus
https://www.readbyqxmd.com/read/29158797/pd-l1-is-a-prognostic-biomarker-in-resected-nsclc-patients-with-moderate-high-smoking-history-and-elevated-serum-scca-level
#15
Lianjing Cao, Xinyue Wang, Shouying Li, Qiongjie Zhi, Yuqian Wang, Liuchun Wang, Kai Li, Richeng Jiang
Programmed cell death-1 (PD-1) -targeted immunotherapy has become a promising treatment paradigm for patients with advanced non-small cell lung cancer (NSCLC). Clinical responses to checkpoint inhibition therapy in NSCLC have been associated with programmed death-1 ligand 1 (PD-L1) expression. However, the association between the expression of PD-L1 and PD-L2 and the clinicopathological features and patient outcomes in NSCLC remain unclear. We retrospectively analyzed 364 patients (158 squamous cell carcinoma and 206 adenocarcinoma) who underwent complete resection between 2009 and 2012...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29158788/programmed-death-ligand-1-pd-l1-expression-in-primary-angiosarcoma
#16
Gerardo Botti, Giosuè Scognamiglio, Laura Marra, Antonio Pizzolorusso, Maurizio Di Bonito, Rossella De Cecio, Monica Cantile, Annarosaria De Chiara
Angiosarcomas are rare malignant endothelial-cell tumors of vascular or lymphatic origin, and are among the most aggressive subtypes of soft-tissue sarcomas. The prognosis is poor and treatment is challenging in many cases. PD-1/PD-L1 pathway plays a critical role in immune escape of tumor cells. Recent studies described that PD-L1 is widely expressed in various types of cancer, providing the basis for the development of PD1/PD-L1 antibodies as anti-cancer immunotherapy. Despite the well-known potential of PD-L1 as prognostic and predictive biomarker, only few studies described its IHC expression in cancer subtypes for the extreme difficulty in developing standard protocol with the different antibody clones available...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29158588/immunotherapy-gut-bacteria-modulate-responses-to-pd-1-blockade
#17
David Killock
No abstract text is available yet for this article.
November 21, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29158368/anti-hu-associated-autoimmune-limbic-encephalitis-in-a-patient-with-pd-1-inhibitor-responsive-myxoid-chondrosarcoma
#18
Kyriakos P Papadopoulos, Rebecca S Romero, Gabriela Gonzalez, James E Dix, Israel Lowy, Matthew Fury
Autoimmune encephalitis is an uncommon complication of immune checkpoint inhibitor therapy. This article reports a case of fatal anti-Hu-associated autoimmune limbic encephalitis presenting within 8 weeks following anti-PD1 therapy in a patient with myxoid chondrosarcoma and pre-existing anti-Hu antibodies. Although tumor reduction occurred in response to PD-1 inhibitor therapy, the patient had a rapidly progressive decline in neurologic function despite initial stabilization with immunosuppression. Considering the increasing use of immune checkpoint inhibitors for the treatment of various malignancies, an increase in the occurrence of neurologic adverse events is likely, requiring prompt intervention and enhanced pharmacovigilance in malignancies associated with onconeuronal antibodies...
November 20, 2017: Oncologist
https://www.readbyqxmd.com/read/29158363/phase-i-pharmacokinetic-study-of-nivolumab-in-korean-patients-with-advanced-solid-tumors
#19
Keun-Wook Lee, Dae Ho Lee, Jin Hyoung Kang, Joon Oh Park, Se Hyun Kim, Yong Sang Hong, Seung Tae Kim, Do-Youn Oh, Yung-Jue Bang
LESSONS LEARNED: This pharmacokinetic study of nivolumab showed that there is little ethnic difference in the handling of nivolumab.Nivolumab was well tolerated in Korean patients. BACKGROUND: This phase I study of nivolumab, an anti-programmed cell death-1 (anti-PD-1) monoclonal antibody, investigated the pharmacokinetics and safety of nivolumab in Korean patients with advanced solid tumors. Findings were compared with results from Japan and the U.S. MATERIALS AND METHODS: In this two-part study, patients received a single dose of nivolumab (1, 3, and 10 mg/kg; ONO-4538-13) and were followed up for 3 weeks...
November 20, 2017: Oncologist
https://www.readbyqxmd.com/read/29157311/peripheral-and-local-predictive-immune-signatures-identified-in-a-phase-ii-trial-of-ipilimumab-with-carboplatin-paclitaxel-in-unresectable-stage-iii-or-stage-iv-melanoma
#20
Rahima Jamal, Réjean Lapointe, Eftihia Cocolakis, Paméla Thébault, Shirin Kazemi, Jennifer E Friedmann, Jeanne Dionne, Jean-François Cailhier, Karl Bélanger, Jean-Pierre Ayoub, Huy Le, Caroline Lambert, Jida El-Hajjar, Léon C van Kempen, Alan Spatz, Wilson H Miller
BACKGROUND: Checkpoint blockade with ipilimumab provides long-term survival to a significant proportion of patients with metastatic melanoma. New approaches to increase survival and to predict which patients will benefit from treatment are needed. This phase II trial combined ipilimumab with carboplatin/paclitaxel (CP) to assess its safety, efficacy, and to search for peripheral and tumor-based predictive biomarkers. METHODS: Thirty patients with untreated unresectable/metastatic melanoma were treated with ipilimumab and CP...
November 21, 2017: Journal for Immunotherapy of Cancer
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