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pd-l1 and cancer

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https://www.readbyqxmd.com/read/29331646/progress-in-the-management-of-advanced-thoracic-malignancies-in-2017
#1
REVIEW
Roberto Ferrara, Laura Mezquita, Benjamin Besse
The treatment paradigm of non-small cell lung cancer (NSCLC) underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival (OS) both in unselected pretreated patients and in untreated patients with PD-L1 expression ≥50%. Furthermore, compelling preliminary results were reported for new combinations of anti-PD-1/PD-L1 agents with chemotherapy or anti-CTLA4 inhibitors. The success of the ICIs appeared to extend to patients with small cell lung cancer (SCLC), mesothelioma or thymic tumors...
January 10, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29330929/adipocytes-affect-castration-resistant-prostate-cancer-cells-to-develop-the-resistance-to-cytotoxic-action-of-nk-cells-with-alterations-of-pd-l1-nkg2d-ligand-levels-in-tumor-cells
#2
Lijun Xu, Mingjing Shen, Xiaodong Chen, Rongying Zhu, Dong-Rong Yang, Ying Tsai, Peter C Keng, Yuhchyau Chen, Soo Ok Lee
BACKGROUND: Obesity affects prostate cancer (PCa) progression, and the periprostatic adipose tissue adjacent to the prostate is considered a driving force of disease progression. Adipocytes are the main cell population in adipose tissues and their paracrine role contributes to PCa progression, however its implication in modulating immune reactions remains largely unknown. We investigated the adipocyte role in controlling the susceptibility of castration-resistant PCa (CRPC) cells to the cytotoxic action of natural killer (NK) cells...
January 12, 2018: Prostate
https://www.readbyqxmd.com/read/29330579/-initially-undetected-de-novo-psoriasis-triggered-by-nivolumab-for-metastatic-base-of-the-tongue-carcinoma
#3
S Troyanova-Slavkova, L Eickenscheidt, K Dumann, L Kowalzick
Nivolumab is a monoclonal antibody that binds to the PD-1 receptor on T cells and inhibits the interaction with the PD-L1 and PD-L2 ligands on cancer cells. Thus, nivolumab has immunostimulatory properties. The known side effects of this therapy include fatigue, skin rash, dysfunction of the thyroid gland and colitis, which are explained by the immunoregulatory mechanisms of the drug. Here we report on the case of a 58-year-old man with metastatic base of tongue carcinoma who developed de novo psoriasis triggered by nivolumab...
January 12, 2018: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/29330552/dosimetry-prediction-for-clinical-translation-of-64cu-pembrolizumab-immunopet-targeting-human-pd-1-expression
#4
Arutselvan Natarajan, Chirag B Patel, Frezghi Habte, Sanjiv S Gambhir
The immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor-infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively quantifying the presence of PD-1 expression in the tumor microenvironment prior to initiation of immune checkpoint blockade may identify the patients likely to respond to therapy. We have developed a 64Cu-pembrolizumab radiotracer and evaluated human dosimetry...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329556/cancer-immunotherapy-beyond-immune-checkpoint-inhibitors
#5
REVIEW
Julian A Marin-Acevedo, Aixa E Soyano, Bhagirathbhai Dholaria, Keith L Knutson, Yanyan Lou
Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized...
January 12, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29328976/pattern-of-programmed-cell-death-ligand-1-expression-and-cd8-positive-t-cell-infiltration-before-and-after-chemoradiotherapy-in-rectal-cancer
#6
Atsushi Ogura, Takashi Akiyoshi, Noriko Yamamoto, Hiroshi Kawachi, Yuichi Ishikawa, Seiichi Mori, Koji Oba, Masato Nagino, Yosuke Fukunaga, Masashi Ueno
BACKGROUND: The synergistic effect of combining immune checkpoint inhibitors with radiotherapy was reported recently, but there are few studies on programmed cell death-ligand 1 (PD-L1) expression in rectal cancer treated by preoperative chemoradiotherapy (CRT). The aim of the present study was to investigate the PD-L1 expression status before and after CRT and its association with clinicopathological characteristics and recurrence in rectal cancer. METHODS: Immunostainings of PD-L1 and CD8 were performed in 287 patients with rectal cancer treated by CRT...
January 9, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29328389/mir-375-inhibits-ifn-%C3%AE-induced-programmed-death-1-ligand%C3%A2-1-surface-expression-in-head-and-neck-squamous-cell-carcinoma-cells-by-blocking-jak2-stat1-signaling
#7
Qingwei Wu, Yingying Zhao, Yiyuan Sun, Xiaojun Yan, Peihua Wang
Upregulation of programmed death 1 ligand 1 (PD-L1) in cancer cells and its ligation to PD-1 on T cells facilitates cancer cell escape from immune surveillance. Therapies with PD-1 or PD-L1 antibodies have resulted in marked clinical responses in various cancer types. Hence, modulators that inhibit PD-L1 expression in cancer cells may serve as a novel strategy by which to enhance host immune responses. In the present study, we investigated the effects of miR-375 on PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) cells by qRT-PCR and western blot analyses...
January 2, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29327160/differences-in-histological-features-and-pd-l1-expression-between-sporadic-microsatellite-instability-and-lynch-syndrome-associated-disease-in-japanese-patients-with-colorectal-cancer
#8
Rin Yamada, Tatsuro Yamaguchi, Takeru Iijima, Rika Wakaume, Misato Takao, Koichi Koizumi, Tsunekazu Hishima, Shin-Ichiro Horiguchi
BACKGROUND: The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients. METHODS: Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis...
January 11, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29327044/association-of-the-lung-immune-prognostic-index-with-immune-checkpoint-inhibitor-outcomes-in-patients-with-advanced-non-small-cell-lung-cancer
#9
Laura Mezquita, Edouard Auclin, Roberto Ferrara, Melinda Charrier, Jordi Remon, David Planchard, Santiago Ponce, Luis Paz Ares, Laura Leroy, Clarisse Audigier-Valette, Enriqueta Felip, Jorge Zerón-Medina, Pilar Garrido, Solenn Brosseau, Gérard Zalcman, Julien Mazieres, Caroline Caramela, Jihene Lahmar, Julien Adam, Nathalie Chaput, Jean Charles Soria, Benjamin Besse
Importance: Derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and lactate dehydrogenase (LDH) level have been correlated with immune checkpoint inhibitor (ICI) outcomes in patients with melanoma. Objective: To determine whether pretreatment dNLR and LDH are associated with resistance to ICIs in patients with advanced non-small cell lung cancer (NSCLC). Design, Setting, and Participants: Multicenter retrospective study with a test (n = 161) and a validation set (n = 305) treated with programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors in 8 European centers, and a control cohort (n = 162) treated with chemotherapy only...
January 11, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29326364/inflammation-and-pd-l1-expression-in-pulmonary-neuroendocrine-tumors
#10
Atsuko Kasajima, Yuichi Ishikawa, Ayaka Iwata, Katja Steiger, Naomi Oka, Hirotaka Ishida, Akira Sakurada, Hiroyoshi Suzuki, Toru Kameya, Björn Konukiewitz, Gunter Kloppel, Yoshinori Okada, Hironobu Sasano, Wilko Weichert
In the light of novel cancer immune therapies, the status of antitumor inflammatory response and its regulation has gained much attention in patients with lung cancer. Ample datasets exist for non-small cell lung cancer, but those for pulmonary neuroendocrine tumors are scarce and controversial. Here, tumor-associated inflammation, CD8+ cell infiltration and PD-L1 status were evaluated in a cohort of 57 resected carcinoids and 185 resected neuroendocrine carcinomas of the lung (58 large cell carcinomas and 127 small cell carcinomas)...
January 11, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29326088/age-effects-of-distinct-immune-checkpoint-blockade-treatments-in-a-mouse-melanoma-model
#11
Álvaro Padrón, Vincent Hurez, Harshita B Gupta, Curtis A Clark, Sri Lakshmi Pandeswara, Bin Yuan, Robert S Svatek, Mary Jo Turk, Justin M Drerup, Rong Li, Tyler J Curiel
Cancer immunotherapy has shown remarkable recent progress. Immune checkpoint blocking antibodies have become the most successful anti-cancer agent class ever developed, with six distinct agents approved since 2011 for a wide variety of cancers. Although age is the biggest risk factor for cancer (aside from selected early-onset pediatric cancers), these agents were tested pre-clinically in young hosts, and there is remarkably little published on the effects of host age on treatment outcomes in pre-clinical studies or human clinical trials...
January 8, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29325739/anti-programmed-cell-death-1-ligand-1-pd-1-pd-l1-antibodies-for-the-treatment-of-urothelial-carcinoma-state-of-the-art-and-future-development
#12
REVIEW
Thomas Powles, Andrea Necchi, Galit Rosen, Subramanian Hariharan, Andrea B Apolo
Immunotherapy with programmed cell death 1/ligand 1 (PD-1/PD-L1) checkpoint inhibitors has expanded a previously limited pool of effective treatment options for patients with metastatic urothelial carcinoma, particularly those with recurring or refractory disease and those who are ineligible for cisplatin. This review reports key findings from completed and ongoing clinical trials that highlight the potential of PD-1/PD-L1 blockade in urothelial carcinoma. A literature search was performed of PubMed, Embase, ClinicalTrials...
December 6, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29325268/-clinical-significance-of-targeting-drug-based-molecular-biomarkers-expression-in-ovarian-clear-cell-carcinoma
#13
M J Li, H R Li, X Cheng, R Bi, X Y Tu, F Liu, L H Chen
Objective: To assess the expression level of targeting drug-based molecular biomarkers in ovarian clear cell carcinoma (OCCC) tissues and its clinical significance. Methods: A total of 63 OCCC patients included 40 primary OCCC and 23 recurrent OCCC for secondary cytoreductive surgery (SCS), who had received primary surgeries at Fudan University Shanghai Cancer Center between January, 2008 and December, 2015 were enrolled, and immunohistochemistry SP method was used to test human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), BRCA2 and programmed death-ligand 1 (PD-L1)protein expression in paraffin-embedded tissues...
December 25, 2017: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/29322798/pd-l1-expression-can-be-regarded-as-prognostic-factor-for-survival-of-non-small-cell-lung-cancer-patients-after-chemoradiotherapy
#14
M Vrankar, M Zwitter, I Kern, K Stanic
Inoperable locally advanced non-small cell lung cancer (LA NSCLC) is treated with concurrent or sequential chemotherapy (ChT) and radiation therapy (RT). Survival rates with this treatment remains poor, reported 5-year survival is about 15%. New treatment strategies, including immunotherapy with programmed death ligand-1 (PD-L1) check point inhibitors are being investigated. The clinical significance of PD-L1 expression in tumor samples from patients with inoperable LA NSCLC who underwent concurrent chemoradiotherapy (CRT) in our institution between 2005 and 2010 was evaluated...
2018: Neoplasma
https://www.readbyqxmd.com/read/29321020/meta-analysis-of-human-gene-expression-in-response-to-mycobacterium-tuberculosis-infection-reveals-potential-therapeutic-targets
#15
Zhang Wang, Seda Arat, Michal Magid-Slav, James R Brown
BACKGROUND: With the global emergence of multi-drug resistant strains of Mycobacterium tuberculosis, new strategies to treat tuberculosis are urgently needed such as therapeutics targeting potential human host factors. RESULTS: Here we performed a statistical meta-analysis of human gene expression in response to both latent and active pulmonary tuberculosis infections from nine published datasets. We found 1655 genes that were significantly differentially expressed during active tuberculosis infection...
January 10, 2018: BMC Systems Biology
https://www.readbyqxmd.com/read/29319049/mechanisms-of-resistance-to-immune-checkpoint-inhibitors
#16
REVIEW
Russell W Jenkins, David A Barbie, Keith T Flaherty
Immune checkpoint inhibitors (ICI) targeting CTLA-4 and the PD-1/PD-L1 axis have shown unprecedented clinical activity in several types of cancer and are rapidly transforming the practice of medical oncology. Whereas cytotoxic chemotherapy and small molecule inhibitors ('targeted therapies') largely act on cancer cells directly, immune checkpoint inhibitors reinvigorate anti-tumour immune responses by disrupting co-inhibitory T-cell signalling. While resistance routinely develops in patients treated with conventional cancer therapies and targeted therapies, durable responses suggestive of long-lasting immunologic memory are commonly seen in large subsets of patients treated with ICI...
January 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29318609/the-efficacy-and-safety-of-anti-pd-1-pd-l1-antibodies-combined-with-chemotherapy-or-ctla4-antibody-as-a-first-line-treatment-for-advanced-lung-cancer
#17
Xiaoling Xu, Zhiyu Huang, Lei Zheng, Yun Fan
Checkpoint inhibitors show promising efficacy in advanced lung cancer, especially in non-small cell lung cancer. This meta-analysis was conducted to explore the therapeutic efficacy and safety of anti-PD-1/PD-L1 antibodies combined with chemotherapy or CTLA4 antibody as first-line treatments for patients with advanced lung cancer. A systematic search was performed in databases for this system review and quantitative meta-analysis. Twelve trials were finally enrolled in the meta-analysis. Our analyses revealed that the combined overall response rate (ORR) and disease control rate (DCR) for immune checkpoint inhibitors combined with chemotherapy for the treatment of non-small cell lung cancer (NSCLC) were 47...
January 10, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29318591/immune-checkpoint-molecules-in-acute-myeloid-leukaemia-managing-the-double-edged-sword
#18
REVIEW
Willemijn Hobo, Tim J A Hutten, Nicolaas P M Schaap, Harry Dolstra
New immunotherapeutic interventions have revolutionized cancer treatment. The immune responsiveness of acute myeloid leukaemia (AML) was first demonstrated by allogeneic stem cell transplantation. In addition, milder immunotherapeutic approaches are exploited. However, the long-term efficacy of these therapies is hampered by various immune resistance and editing mechanisms. In this regard, co-inhibitory signalling pathways have been shown to play a crucial role. Via up-regulation of inhibitory checkpoints, tumour-reactive T cell and Natural Killer cell responses can be strongly impeded...
January 9, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29317703/modeling-tumor-immunity-of-mouse-glioblastoma-by-exhausted-cd8-t-cells
#19
Hiroshi Nakashima, Quazim A Alayo, Pablo Penaloza-MacMaster, Gordon J Freeman, Vijay K Kuchroo, David A Reardon, Soledad Fernandez, Michael Caligiuri, E Antonio Chiocca
T cell exhaustion occurs during chronic infection and cancers. Programmed cell death protein-1 (PD-1) is a major inhibitory checkpoint receptor involved in T cell exhaustion. Blocking antibodies (Abs) against PD-1 or its ligand, PD-L1, have been shown to reverse T cell exhaustion during chronic infection and cancers, leading to improved control of persistent antigen. However, modeling tumor-specific T cell responses in mouse has been difficult due to the lack of reagents to detect and phenotype tumor-specific immune responses...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29313208/perspective-on-immune-oncology-with-liquid-biopsy-peripheral-blood-mononuclear-cells-and-microbiome-with-non-invasive-biomarkers-in-cancer-patients
#20
REVIEW
A Mitsuhashi, Y Okuma
Antibodies against immune checkpoint inhibitors such as anti-programmed cell death protein 1 (PD-1) and anti-programmed death ligand 1 (PD-L1) play a key role in the treatment of advanced lung cancer. To examine the clinical benefits of these agents, preclinical and clinical studies have been conducted to identify definitive biomarkers associated with cancer status. Analysis of the blood and feces of tumor patients has attracted attention in recent studies attempting to identify non-invasive biomarkers such as cytokines, soluble PD-L1, peripheral blood mononuclear cells, and gut microbiota...
January 8, 2018: Clinical & Translational Oncology
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