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pd-l1 and cancer

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https://www.readbyqxmd.com/read/29168430/triple-negative-breast-cancer-prognostic-role-of-immune-related-factors-a-systematic-review
#1
Elisabeth Specht Stovgaard, Dorte Nielsen, Estrid Hogdall, Eva Balslev
PURPOSE: Treatment of breast cancer has been increasingly successful in recent years with the advent of HER2-receptor targeted treatment and endocrine treatment. However, the triple negative subgroup of breast cancer (TNBC) (estrogen-, progesterone- and HER2-receptor negative) still lacks targeted treatment options. TNBC is a type of breast cancer that often affects younger women, and generally has a worse prognosis than other types of breast cancer. Recently, the complex role of the immune system in cancer growth, elimination and metastasis has been the object of increased attention...
November 23, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29168339/prognostic-value-of-pd-l1-expression-in-combination-with-cd8-tils-density-in-patients-with-surgically-resected-non-small-cell-lung-cancer
#2
Hui Yang, Jinpeng Shi, Dongmei Lin, Xuefei Li, Chao Zhao, Qi Wang, Limin Zhang, Tao Jiang, Sha Zhao, Xiaozhen Liu, Yijun Jia, Yajun Zhang, Weijing Cai, Caicun Zhou
To investigate the prognostic value of PD-L1 expression combined with CD8(+) TILs density in patients with resected NSCLC and correlations with clinicopathological features. We retrospectively enrolled 178 patients with resected NSCLC from 2011 to 2015. All surgical primary and 58 matched metastatic lymph node specimens were tested for PD-L1, CD8(+) TILs, and oncogenic alterations. PD-L1(+) was detected in 71 (39.9%) and CD8(high) TILs in 74 (41.6%) cases. Smoking, SqCC, and EGFR(-) were associated with both PD-L1(+) and CD8(high) TILs...
November 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29167175/signaling-pathways-and-immune-evasion-mechanisms-in-classical-hodgkin-lymphoma
#3
W Robert Liu, Margaret A Shipp
Classical Hodgkin lymphoma (cHL) is an unusual B-cell derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/ immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis of immune evasion - near uniform copy number alterations (CNAs) of chromosome 9p24...
November 22, 2017: Blood
https://www.readbyqxmd.com/read/29167009/-advances-of-the-role-of-lung-cancer-driver-gene-and-pd-1-pd-l1-pathway-interaction-in-the-tumorigenesis-and-progression-of-non-small-cell-lung-cancer
#4
Yan Shi, Wang Lv, Luming Wang, Jian Hu
Programmed death 1 (PD-1) and programmed death 1 ligand (PD-L1) pathway is a key mechanism of immune regulation, and its abnormal activation in tumor tissues suggests that PD-1/PD-L1 pathway may participate in the regulation of tumor immune escape. Driver gene mutation which is known as a key factor in the tumorigenesis of non-small cell lung cancer (NSCLC), was also reported to play a important role in the process of tumor immune escape. It indicates that there is an interaction between driver gene and PD-1/PD-L1 pathway...
November 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29167005/-distribution-and-clinical-significance-of-ctla-4-pd-1-and-pd-l1-in-peripheral-blood-of-patients-with-small-cell-lung-cancer
#5
Hui Li, Yan Liu, Ying Liu, Jingjing Liu, Dandan Zhao, Ying Wang, Ying Cheng
BACKGROUND: The aim of this study is to explore cytotoxic T lymphocyte associated antigen 4 (CTLA-4), programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) distribution and clinical value in liquid biopsy (such as blood) of small cell lung cancer (SCLC) patients. METHODS: A total of 60 healthy and 290 chemotherapy-naive patients with SCLC were recruited. Venous blood samples were collected prior to chemotherapy (baseline) and after the second cycle of chemotherapy (2nd cycle), and flow cytometry was used to analyze the level of CTLA-4, PD-1 or PD-L1 with or without CD3, CD4, CD8 or CD25...
November 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29165286/chemoradiation-induced-alteration-of-programmed-death-ligand-1-and-cd8-tumor-infiltrating-lymphocytes-identified-patients-with-poor-prognosis-in-rectal-cancer-a%C3%A2-matched-comparison-analysis
#6
Yu Jin Lim, Jaemoon Koh, Sehui Kim, Sang-Rok Jeon, Eui Kyu Chie, Kyubo Kim, Gyeong Hoon Kang, Sae-Won Han, Tae-You Kim, Seung-Yong Jeong, Kyu Joo Park, Hong-Gyun Wu
PURPOSE: To evaluate chemoradiotherapy (CRT)-induced changes in the expression levels of programmed death-ligand 1 (PD-L1) and CD8(+) tumor-infiltrating lymphocytes (TILs) and prognostic associations in rectal cancer. METHODS AND MATERIALS: We performed a paired analysis using pre-CRT biopsies and the corresponding post-CRT resected tissues of 123 rectal cancer patients undergoing preoperative CRT followed by surgery between 2005 and 2012. Immunohistochemistry of PD-L1 and CD8 was analyzed for the specimens...
December 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29163851/checkpoint-inhibitors-in-endometrial-cancer-preclinical-rationale-and-clinical-activity
#7
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/29163822/structural-basis-of-the-therapeutic-anti-pd-l1-antibody-atezolizumab
#8
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/29163815/pd-l1-expression-heterogeneity-in-non-small-cell-lung-cancer-evaluation-of-small-biopsies-reliability
#9
Enrico Munari, Giuseppe Zamboni, Marcella Marconi, Marco Sommaggio, Matteo Brunelli, Guido Martignoni, George J Netto, Francesca Moretta, Maria Cristina Mingari, Matteo Salgarello, Alberto Terzi, Vincenzo Picece, Carlo Pomari, Gianluigi Lunardi, Alberto Cavazza, Giulio Rossi, Lorenzo Moretta, Giuseppe Bogina
Immunotherapy with checkpoint inhibitors, allowing recovery of effector cells function, has demonstrated to be highly effective in many tumor types and represents a true revolution in oncology. Recently, the anti-PD1 agent pembrolizumab was granted FDA approval for the first line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors show PD-L1 expression in ≥ 50% of neoplastic cells and as a second line treatment for patients with NSCLC expressing PD-L1 in ≥1% of neoplastic cells, evaluated with a validated assay...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163797/pd-l1-expression-on-immune-cells-is-a-favorable-prognostic-factor-for-vulvar-squamous-cell-carcinoma-patients
#10
Jacek J Sznurkowski, Anton Żawrocki, Katarzyna Sznurkowska, Rafał Pęksa, Wojciech Biernat
Background: Anti-immune programmed death-ligand 1 (PD-L1) pathway is used by the tumor to overcome immune system and serves as immunotherapy target in various malignancies. Aim: To investigate the expression of PD-L1 in vulvar squamous cell carcinoma (vSCC) and to assess it's clinicopathological and prognostic significance. Methods: Immunohistochemical PD-L1 expression was evaluated in 84 vSCCs with previously defined status of p16 and DNA-HPV, infiltration of immune cells: CD8+, CD4+, FOXP3+, CD56+, CD68+, and GZB+ cells...
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
#11
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
#12
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/29163540/local-high-dose-radiotherapy-induces-systemic-immunomodulating-effects-of-potential-therapeutic-relevance-in-oligometastatic-breast-cancer
#13
Elena Muraro, Carlo Furlan, Michele Avanzo, Debora Martorelli, Elisa Comaro, Aurora Rizzo, Damiana A Fae', Massimiliano Berretta, Loredana Militello, Alessandro Del Conte, Simon Spazzapan, Riccardo Dolcetti, Marco Trovo'
Local irradiation of cancer through radiotherapy can induce spontaneous regression of non-directly irradiated lesions, suggesting the involvement of systemic antitumor immune responses. In oligometastatic breast cancer (BC) patients, the use of stereotactic body radiotherapy (SBRT) favors the local control of treated lesions and may contribute to break local tolerance and release tumor-associated antigens (TAAs), improving host antitumor immunity. We performed a detailed immunomonitoring of BC patients undergoing SBRT to verify its ability to "switch on" the anti-tumor immunity both systemically, in peripheral blood, and locally, employing in vitro BC models...
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
#14
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/29160310/cyclin-d-cdk4-kinase-destabilizes-pd-l1-via-cul3-spop-to-control-cancer-immune-surveillance
#15
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/29158797/pd-l1-is-a-prognostic-biomarker-in-resected-nsclc-patients-with-moderate-high-smoking-history-and-elevated-serum-scca-level
#16
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/29158791/correlation-of-cancer-stem-cell-markers-and-immune-cell-markers-in-resected-non-small-cell-lung-cancer
#17
Zhaoqin Huang, Haining Yu, Jianbo Zhang, Haiyan Jing, Wanqi Zhu, Xiaolin Li, Lingling Kong, Ligang Xing, Jinming Yu, Xiangjiao Meng
Background: Recent studies confirmed that immunotherapy showed prominent efficacy in non-small cell lung cancer (NSCLC). Cancer stem cells/cancer initiating cells are resistant to anticancer treatment. The purpose of the study was to analyze the correlation of cancer stem cells/cancer initiating cells and tumor-infiltrating immune cells in NSCLC. Methods: CD133, octamer 4 (OCT-4), CD8, CD56, human leukocyte antigen (HLA) class I and programmed death ligand-1 (PD-L1) were assessed in 172 resected NSCLC samples...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29158788/programmed-death-ligand-1-pd-l1-expression-in-primary-angiosarcoma
#18
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/29157298/impressive-response-to-immunotherapy-in-a-metastatic-gastric-cancer-patient-could-somatic-copy-number-alterations-help-patient-selection
#19
Gustavo Dos Santos Fernandes, Daniel da Motta Girardi, Luiza Dib Batista Bugiato Faria, João Paulo Giacomini Bernardes, Renata de Almeida Coudry
BACKGROUND: Metastatic gastric cancer (GC) is an incurable and aggressive disease with a poor prognosis. Immunotherapy is an attractive approach for treating patients with cancer, and studies using immunotherapy have shown promising results in melanoma, kidney and non-small cell lung cancers, among others. CASE PRESENTATION: We present a case of a 50-year-old woman with metastatic GC whose cancer had progressed after first-line chemotherapy and who received pembrolizumab as an experimental treatment...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29157296/biomarkers-for-immunotherapy-in-bladder-cancer-a-moving-target
#20
REVIEW
David H Aggen, Charles G Drake
Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U...
November 21, 2017: Journal for Immunotherapy of Cancer
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