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https://www.readbyqxmd.com/read/27930644/immunotherapy-for-the-treatment-of-breast-cancer-checkpoint-blockade-cancer-vaccines-and-future-directions-in-combination-immunotherapy
#1
Heather L McArthur, David B Page
Immunotherapy encompasses both vaccines that direct immune responses to tumor-associated antigens, and checkpoint blocking antibodies that inhibit immune system suppression by targeting key pathways mediated by cytotoxic T-lymphocyte-associated antigen 4, programmed death 1 (PD-1), and programmed death ligand 1 (PD-L1). Both of these approaches currently are being explored as potential strategies for the treatment of breast cancer. Recent studies suggest that immunotherapy is poised to change the therapeutic landscape for some breast cancers...
November 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/27925176/pd-l1-expression-of-the-residual-tumor-serves-as-a-prognostic-marker-in-local-advanced-breast-cancer-after-neoadjuvant-chemotherapy
#2
Sheng Chen, Ruo-Xi Wang, Yin Liu, Wen-Tao Yang, Zhi-Ming Shao
This study sought to investigate the prevalence of programmed death ligand 1 (PD-L1) and its prognostic value in patients with residual tumors after neoadjuvant chemotherapy (NCT) for locally advanced breast cancer (LABC). A total of 309 patients considered as non-pathological complete responders (non-pCR) after NCT followed by mastectomy were selected. The expression of PD-L1 and tumor-infiltrating lymphocytes (TILs) in residual breast cancer cells was assessed by immunohistochemistry in surgical specimens...
December 7, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27912781/an-immune-stratification-reveals-a-subset-of-pd-1-lag-3-double-positive-triple-negative-breast-cancers
#3
Giulia Bottai, Carlotta Raschioni, Agnese Losurdo, Luca Di Tommaso, Corrado Tinterri, Rosalba Torrisi, Jorge S Reis-Filho, Massimo Roncalli, Christos Sotiriou, Armando Santoro, Alberto Mantovani, Sherene Loi, Libero Santarpia
BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC. METHODS: Formalin-fixed, paraffin-embedded tissues were retrospectively collected from a cohort of patients with early-stage TNBC treated with adjuvant anthracycline-based chemotherapy (n = 259)...
December 3, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27889782/molecular-pathology-a-requirement-for-precision-medicine-in-cancer
#4
Manfred Dietel
The increasing importance of targeting drugs and check-point inhibitors in the treatment of several tumor entities (breast, colon, lung, malignant melanoma, lymphoma, etc.) and the necessity of a companion diagnostic (HER2, (pan)RAS, EGFR, ALK, BRAF, ROS1, MET, PD-L1, etc.) is leading to new challenges for surgical pathology. Since almost all the biomarkers to be specifically detected are tissue based, a precise and reliable diagnostic is absolutely crucial. To meet this challenge surgical pathology has adapted a number of molecular methods (semi-quantitative immunohistochemistry, fluorescence in situ hybridization, PCR and its multiple variants, (pyro/Sanger) sequencing, next generation sequencing (amplicon, whole exome, whole genome), DNA arrays, methylation analyses, etc...
2016: Oncology Research and Treatment
https://www.readbyqxmd.com/read/27870715/posttranscriptional-control-of-pd-l1-expression-by-17%C3%AE-estradiol-via-pi3k-akt-signaling-pathway-in-er%C3%AE-positive-cancer-cell-lines
#5
Lingyun Yang, Feng Huang, Jiandong Mei, Xun Wang, Qiuyang Zhang, Hongjing Wang, Mingrong Xi, Zongbing You
OBJECTIVE: Estrogen is a well-known oncogenic driver in endometrial (ECs) and breast cancers (BCs). Programmed cell death protein 1 (PD-1) and its ligands PD-1 Ligand 1 (PD-L1) and PD-L2 have been shown to mediate immune evasion of the tumor cells. The purpose of the present study was to assess the effects of estrogen on PD-L1 and PD-L2 expression in EC and BC cell lines. METHODS: 17β-Estradiol (E2)-induced expression of PD-L1 and PD-L2 and possible signaling pathway were investigated in EC and BC cells...
November 17, 2016: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/27801993/predictive-factors-of-tumor-immune-microenvironment-for-long-term-follow-up-in-early-stage-breast-cancer
#6
Mina Okabe, Uhi Toh, Nobutaka Iwakuma, Shuko Saku, Momoko Akashi, Yuko Kimitsuki, Naoko Seki, Akihiko Kawahara, Etsuyo Ogo, Kyogo Itoh, Yoshito Akagi
To investigate the correlation of immunologic factors in the tumor environment of breast cancer, using immunohistological staining to evaluate the expression of PD-1/PD-L1, PTEN, TILs and macrophages, and to analyze the association between the immunologic factors and clinical outcome for patients with early stage breast cancer (EBC). A total of ninety-seven EBC patients who underwent standard surgery were investigated. PD-1/PD-L1, PTEN expression and the density of CD3+ TILs, CD8+ TILs, and CD163+ macrophages were evaluated by immunohistochemical analysis...
November 1, 2016: Cancer Science
https://www.readbyqxmd.com/read/27793883/immune-blockade-inhibition-in-breast-cancer
#7
REVIEW
Ioannis A Voutsadakis
Besides limited success in treatment of melanoma and renal cell carcinoma, immune treatments of cancer (cancer immunotherapy) had not until recently met the great expectations associated with them over the years. This failure appears now to be reversed with the introduction of checkpoint (immune blockade) inhibitors. Two receptor-ligand checkpoint inhibition pairs, the one based on the inhibition of inhibitory receptor cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and the other based on the inhibition of the programmed death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pair have entered the clinical arena...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27785100/current-advances-in-biomarkers-for-targeted-therapy-in-triple-negative-breast-cancer
#8
REVIEW
Brett Fleisher, Charlotte Clarke, Sihem Ait-Oudhia
Triple-negative breast cancer (TNBC) is a complex heterogeneous disease characterized by the absence of three hallmark receptors: human epidermal growth factor receptor 2, estrogen receptor, and progesterone receptor. Compared to other breast cancer subtypes, TNBC is more aggressive, has a higher prevalence in African-Americans, and more frequently affects younger patients. Currently, TNBC lacks clinically accepted targets for tailored therapy, warranting the need for candidate biomarkers. BiomarkerBase, an online platform used to find biomarkers reported in clinical trials, was utilized to screen all potential biomarkers for TNBC and select only the ones registered in completed TNBC trials through clinicaltrials...
2016: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/27777769/clinical-significance-of-tumor-infiltrating-lymphocytes-in-breast-cancer
#9
Sasha E Stanton, Mary L Disis
Tumor infiltrating lymphocytes (TIL) play an essential role in mediating response to chemotherapy and improving clinical outcomes in all subtypes of breast cancer. Triple negative breast cancers (TN) are most likely to have tumors with >50 % lymphocytic infiltrate, termed lymphocyte predominant breast cancer, and derive the greatest survival benefit from each 10 % increase in TIL. The majority of HER2(+) breast cancers have similar level of immune infiltrate as TN breast cancer yet the presence of TILs has not shown the same survival benefit...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27766079/restoring-lost-anti-her-2-th1-immunity-in-breast-cancer-a-crucial-role-for-th1-cytokines-in-therapy-and-prevention
#10
Nadia F Nocera, M Catherine Lee, Lucy M De La Cruz, Cinthia Rosemblit, Brian J Czerniecki
The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27762298/pd-l1-is-a-critical-mediator-of-regulatory-b-cells-and-t-cells-in-invasive-breast-cancer
#11
Honggeng Guan, Yuqiu Wan, Jing Lan, Qin Wang, Zhangyu Wang, Yecheng Li, Jiqing Zheng, Xueguang Zhang, Zemin Wang, Yueping Shen, Fang Xie
Regulatory T cells (Tregs), a key mediator in regulating anti-tumor immune suppression, tumor immune escape, metastasis and relapse, are considered an important therapeutic target in immunotherapy of human cancers. In the present investigation, elevated CD19(+) CD24(+) CD38(+) regulatory B cells (Bregs) were observed in PBMCs of invasive carcinoma of breast (IBCa) patients compared with that in patients with fibroadenoma (FIBma) or healthy individuals, and the positive correlation existed between Bregs and CD4(+) CD25(+) CD127(-) Tregs (r = 0...
October 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27755140/targeting-the-host-immune-system-pd-1-and-pd-l1-antibodies-and-breast-cancer
#12
Shaheenah Dawood, Hope S Rugo
PURPOSE OF REVIEW: This article describes the role of the PD-1 axis and reviews current data and future directions inhibiting PD-1 and PD-L1 in breast cancer. RECENT FINDINGS: Four phase I monotherapy expansion trials in patients with metastatic breast cancer have demonstrated low but durable single agent responses to PD-1 and PD-L1 inhibitors, ranging from 4.8 to 19%. Higher response rates are seen in triple negative breast cancer, compared with hormone receptor positive disease...
October 15, 2016: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/27727484/comparison-of-tumour-infiltrating-lymphocytes-between-primary-and-metastatic-tumours-in-breast-cancer-patients
#13
Rin Ogiya, Naoki Niikura, Nobue Kumaki, Giampaolo Bianchini, Shigehisa Kitano, Takayuki Iwamoto, Naoki Hayashi, Kozue Yokoyama, Risa Oshitanai, Mayako Terao, Toru Morioka, Banri Tsuda, Takuho Okamura, Yuki Saito, Yasuhiro Suzuki, Yutaka Tokuda
The presence of tumour-infiltrating lymphocytes (TILs) is associated with favourable long-term outcome in breast cancer. However, little is known about changes in TILs during metastatic progression. To confirm our hypothesis that malignant tumours escape from the host immune system during metastasis, we evaluated the percentage of TILs in paired samples of primary and metastatic breast tumours. We retrospectively identified 25 patients with human epidermal growth factor receptor-2 (HER2)-positive (n = 14, HER2+) and triple negative (n = 11, TN) early breast cancer diagnosed during 1990-2009 at Tokai University Hospital and who subsequently experienced regional or distant recurrence confirmed by tumour biopsy/resection...
October 11, 2016: Cancer Science
https://www.readbyqxmd.com/read/27721873/expression-of-programmed-death-receptor-ligand-1-with-high-tumor-infiltrating-lymphocytes-is-associated-with-better-prognosis-in-breast-cancer
#14
Sang Byung Bae, Hyun Deuk Cho, Mee-Hye Oh, Ji-Hye Lee, Si-Hyong Jang, Soon Auck Hong, Junhun Cho, Sung Yong Kim, Sun Wook Han, Jong Eun Lee, Han Jo Kim, Hyun Ju Lee
PURPOSE: The interaction of programmed death receptor 1 (PD-1) and its ligand, programmed death receptor ligand 1 (PD-L1), negatively regulates immune responses. This study aimed to clarify PD-L1 expression levels in breast cancer through immunohistochemistry (IHC) and to evaluate associations between these findings and clinicopathologic variables, including prognosis. METHODS: PD-L1 expression was analyzed using IHC on tissue microarrays of 465 invasive breast carcinomas...
September 2016: Journal of Breast Cancer
https://www.readbyqxmd.com/read/27707838/activation-of-sting-dependent-innate-immune-signaling-by-s-phase-specific-dna-damage-in-breast-cancer
#15
Eileen E Parkes, Steven M Walker, Laura E Taggart, Nuala McCabe, Laura A Knight, Richard Wilkinson, Karen D McCloskey, Niamh E Buckley, Kienan I Savage, Manuel Salto-Tellez, Stephen McQuaid, Mary T Harte, Paul B Mullan, D Paul Harkin, Richard D Kennedy
BACKGROUND: Previously we identified a DNA damage response-deficient (DDRD) molecular subtype within breast cancer. A 44-gene assay identifying this subtype was validated as predicting benefit from DNA-damaging chemotherapy. This subtype was defined by interferon signaling. In this study, we address the mechanism of this immune response and its possible clinical significance. METHODS: We used immunohistochemistry (IHC) to characterize immune infiltration in 184 breast cancer samples, of which 65 were within the DDRD subtype...
January 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/27686176/stromal-pd-l1-expression-is-associated-with-better-disease-free-survival-in-triple-negative-breast-cancer
#16
Xiaoxian Li, Ceyda Sonmez Wetherilt, Uma Krishnamurti, Jing Yang, Yamin Ma, Toncred M Styblo, Jane L Meisel, Limin Peng, Momin T Siddiqui, Cynthia Cohen, Ritu Aneja
OBJECTIVES: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, and there is no approved targeted therapy. We studied the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in TNBC. METHODS: Full-face sections from 136 TNBC cases without neoadjuvant therapy between 2004 and 2013 were stained and evaluated for immune cell PD-1 staining and stromal or tumoral PD-L1 staining using the H-score (staining percentage × intensity)...
October 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27651308/efficacy-of-cotargeting-angiopoietin-2-and-the-vegf-pathway-in-the-adjuvant-postsurgical-setting-for-early-breast-colorectal-and-renal-cancers
#17
Florence T H Wu, Shan Man, Ping Xu, Annabelle Chow, Marta Paez-Ribes, Christina R Lee, Steven R Pirie-Shepherd, Urban Emmenegger, Robert S Kerbel
Antiangiogenic tyrosine kinase inhibitors (TKI) that target VEGF receptor-2 (VEGFR2) have not been effective as adjuvant treatments for micrometastatic disease in phase III clinical trials. Angiopoietin-2 (Ang2) is a proangiogenic and proinflammatory vascular destabilizer that cooperates with VEGF. The purpose of this study was to test whether CVX-060 (an Ang2-specific CovX-body) can be combined with VEGFR2-targeting TKIs (sunitinib or regorafenib) to successfully treat postsurgical metastatic disease in multiple orthotopically implanted human tumor xenograft and syngeneic murine tumor models...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27574444/pd-l1-expression-in-human-cancers-and-its-association-with-clinical-outcomes
#18
REVIEW
Xin Wang, Feifei Teng, Li Kong, Jinming Yu
PD-L1 is an immunoinhibitory molecule that suppresses the activation of T cells, leading to the progression of tumors. Overexpression of PD-L1 in cancers such as gastric cancer, hepatocellular carcinoma, renal cell carcinoma, esophageal cancer, pancreatic cancer, ovarian cancer, and bladder cancer is associated with poor clinical outcomes. In contrast, PD-L1 expression correlates with better clinical outcomes in breast cancer and merkel cell carcinoma. The prognostic value of PD-L1 expression in lung cancer, colorectal cancer, and melanoma is controversial...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27572267/glycosylation-and-stabilization-of-programmed-death-ligand-1-suppresses-t-cell-activity
#19
Chia-Wei Li, Seung-Oe Lim, Weiya Xia, Heng-Huan Lee, Li-Chuan Chan, Chu-Wei Kuo, Kay-Hooi Khoo, Shih-Shin Chang, Jong-Ho Cha, Taewan Kim, Jennifer L Hsu, Yun Wu, Jung-Mao Hsu, Hirohito Yamaguchi, Qingqing Ding, Yan Wang, Jun Yao, Cheng-Chung Lee, Hsing-Ju Wu, Aysegul A Sahin, James P Allison, Dihua Yu, Gabriel N Hortobagyi, Mien-Chie Hung
Extracellular interaction between programmed death ligand-1 (PD-L1) and programmed cell death protein-1 (PD-1) leads to tumour-associated immune escape. Here we show that the immunosuppression activity of PD-L1 is stringently modulated by ubiquitination and N-glycosylation. We show that glycogen synthase kinase 3β (GSK3β) interacts with PD-L1 and induces phosphorylation-dependent proteasome degradation of PD-L1 by β-TrCP. In-depth analysis of PD-L1 N192, N200 and N219 glycosylation suggests that glycosylation antagonizes GSK3β binding...
August 30, 2016: Nature Communications
https://www.readbyqxmd.com/read/27531819/comprehensive-profiling-of-metaplastic-breast-carcinomas-reveals-frequent-overexpression-of-programmed-death-ligand-1
#20
Upasana Joneja, Semir Vranic, Jeffrey Swensen, Rebecca Feldman, Wangjuh Chen, Jeffrey Kimbrough, Nianqing Xiao, Sandeep Reddy, Juan Palazzo, Zoran Gatalica
AIMS: Metaplastic breast carcinoma (MBC) is a rare subtype of breast carcinoma less responsive to conventional chemotherapy than ductal carcinoma. In molecular terms, MBCs usually cluster with triple-negative breast cancers (TNBCs), but have a worse prognosis than TNBCs. Studies investigating MBCs for specific biomarkers of therapy response are rare and limited by the methodological approaches. The aim of the present study was to characterise MBCs on a molecular level and test programmed death-ligand 1 (PD-L1) biomarker expression in MBCs for future therapeutic interventions...
August 16, 2016: Journal of Clinical Pathology
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