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Pd-l1 breast cancer

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https://www.readbyqxmd.com/read/28916815/programmed-death-ligand-1-pd-l1-expression-in-tumour-cell-and-tumour-infiltrating-lymphocytes-of-her2-positive-breast-cancer-and-its-prognostic-value
#1
Ahrong Kim, So Jeong Lee, Young Keum Kim, Won Young Park, Do Youn Park, Jee Yeon Kim, Chang Hun Lee, Gyungyub Gong, Gi Yeong Huh, Kyung Un Choi
Immunotherapy targeting PD-1/PD-L1 axis showed benefits in cancer. Prognostic significance of tumour infiltrating lymphocytes (TILs) has been determined. We evaluated PD-L1 protein expression in tumour cells and TILs, PD-L1 mRNA level and various histopathologic factors including TILs using 167 formalin-fixed paraffin embedded tissues and 39 fresh tissue of HER2-positive breast cancer. TILs level and PD-L1 expression in tumour cells and TILs were significantly correlated one another. PD-L1 positivity in tumour cells was associated with high histologic grade and high TILs level (p < 0...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28914717/the-relationship-between-mismatch-repair-deficiency-and-pd-l1-expression-in-breast-carcinoma
#2
Anne M Mills, Erik A Dill, Christopher A Moskaluk, Jaroslaw Dziegielewski, Tim N Bullock, Patrick M Dillon
Mismatch repair (MMR) deficiency in solid tumors has recently been linked to susceptibility to immunotherapies targeting the programmed cell death-1 (PD-1)/programmed cell death-1 ligand (PD-L1) axis. Loss of MMR proteins has been shown to correlate with tumoral PD-L1 expression in colorectal and endometrial carcinomas, but the association between expression of MMR proteins and PD-L1 has not previously been studied in breast carcinoma, where MMR deficiency is less common. We assessed the relationship between PD-L1 and MMR protein expression by immunohistochemistry in 245 primary and 40 metastatic breast carcinomas...
September 13, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28913723/therapeutic-implications-of-the-molecular-and-immune-landscape-of-triple-negative-breast-cancer
#3
REVIEW
Ana C Gregório, Manuela Lacerda, Paulo Figueiredo, Sérgio Simões, Sérgio Dias, João Nuno Moreira
Treatment and management of breast cancer imposes a heavy burden on public health care, and incidence rates continue to increase. Breast cancer is the most common female neoplasia and primary cause of death among women worldwide. The recognition of breast cancer as a complex and heterogeneous disease, comprising different molecular entities, was a landmark in our understanding of this malignancy. Valuing the impact of the molecular characteristics on tumor behavior enabled a better assessment of a patient's prognosis and increased the predictive power to therapeutic response and clinical outcome...
September 14, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28912897/genomic-analysis-of-tumor-microenvironment-immune-types-across-14-solid-cancer-types-immunotherapeutic-implications
#4
Yu-Pei Chen, Yu Zhang, Jia-Wei Lv, Ying-Qin Li, Ya-Qin Wang, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Yan-Ping Mao, Jing-Ping Yun, Na Liu, Jun Ma
We performed a comprehensive immuno-genomic analysis of tumor microenvironment immune types (TMITs), which is classified into four groups based on PD-L1+CD8A or PD-L1+cytolytic activity (CYT) expression, across a broad spectrum of solid tumors in order to help identify patients who will benefit from anti- PD-1/PD-L1 therapy. The mRNA sequencing data from The Cancer Genome Atlas (TCGA) of 14 solid cancer types representing 6,685 tumor samples was analyzed. TMIT was classified only for those tumor types that both PD-L1 and CD8A/CYT could prefict mutation and/or neoantigen number...
2017: Theranostics
https://www.readbyqxmd.com/read/28894845/relationship-between-pd-l1-expression-and-clinical-characteristics-in-patients-with-breast-invasive-ductal-carcinoma
#5
Jian Lou, Yuefen Zhou, Jianhui Huang, Xiaojun Qian
OBJECTIVE: To evaluate the expression of PD-L1 (programmed death 1 ligand 1, PD-L1) and its clinical significance in breast invasive ductal carcinoma. METHODS: Tumor samples were collected from 64 cases of breast invasive ductal carcinoma patients, and tumor adjacent normal breast tissue were obtained as normal control. The expression of PD-L1 were examined by immunohistochemical staining and real time PCR assay, its correlations with patients' clinical pathological characteristics were analyzed...
2017: Open Medicine (Warsaw, Poland)
https://www.readbyqxmd.com/read/28881675/pd-l1-and-intratumoral-immune-response-in-breast-cancer
#6
Zhi-Qiang Wang, Katy Milne, Heather Derocher, John R Webb, Brad H Nelson, Peter H Watson
PURPOSE: PD-L1 is thought to play an important role in the antitumor immune response. In this study, we investigated the expression of PD-L1 within breast tumor subsets to better define its prognostic significance. METHODS: Immunohistochemistry was performed to determine PD-L1 tumor cell expression and to enumerate CD8, CD4 and CD68 tumor-infiltrating leucocytes (TIL) in a cohort of 443 breast cancers categorized by molecular subtype. RESULTS: Across the entire cohort, PD-L1 tumor cell expression was observed in 73/443 (16...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28869441/improvement-of-cytotoxicity-of-autologous-ciks-from-patients-with-breast-cancer-to-mcf-7-cells-by-suppressed-pd-1-expression
#7
Li-Wei Liu, Ming-Ya Yang, Min Zhou, Jia-Jia Li, Bo Liu, Yue-Yin Pan
OBJECTIVE: To investigate the improvement of cytotoxicity of autologous CIKs from patients with breast cancer to MCF-7 cells by suppressed PD-1 expression. METHODS: The Lentiviral Vector/PD-1 carrying the gene that can suppressed PD-1 was transferred to CIK cells from patients with breast cancer to inhibit PD-1 expression. The PD-1 protein were detected by RT-PCR and Western blot. The positive PD-1 of CIKs and PD-L1 of MCF-7 cells were detected by FCM, and cytotoxicity of CIKs to MCF-7 was assayed by CCK-8...
August 25, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28855210/cd73-promotes-resistance-to-her2-erbb2-antibody-therapy
#8
Martin Turcotte, David Allard, Deepak Mittal, Yacine Bareche, Laurence Buisseret, Vinu Jose, Sandra Pommey, Vincent Delisle, Sherene Loi, Heikki Joensuu, Pirkko-Liisa Kellokumpu-Lehtinen, Christos Sotiriou, Mark J Smyth, John Stagg
Expression of the ectonucleotidase CD73 by tumor cells, stromal cells, and immune cells is associated in cancer with immune suppression. In this study, we investigated the role of CD73 on the activity of the anti-HER2/ErbB2 monoclonal antibody (mAb) trastuzumab. In a prospective randomized phase III clinical trial evaluating the activity of trastuzumab, high levels of CD73 gene expression associated significantly with poor clinical outcome. In contrast, high levels of PD-1 and PD-L1 associated with improved clinical outcome...
August 30, 2017: Cancer Research
https://www.readbyqxmd.com/read/28843709/pd-l1-in-breast-cancer-comparative-analysis-of-three-different-antibodies
#9
Tejashree Karnik, Bruce F Kimler, Fang Fan, Ossama Tawfik
The Programmed cell death-1 and its ligand-1 (PD-L1) interaction serve as a regulatory check against excessive immune response to antigen and autoimmunity. We compared the performance of three different PD-L1 antibodies (Ventana SP263, Dako 22C3 and BioCare RbMCAL10 antibodies) in 136 invasive ductal carcinoma specimens including 43 primary, 48 locally metastatic and 46 distantly metastatic disease. PD-L1 expression was correlated with clinicopathologic parameters including tumor size, grade, lymphovascular invasion, estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki67, molecular type, TN status...
August 23, 2017: Human Pathology
https://www.readbyqxmd.com/read/28819027/combination-therapy-with-bispecific-antibodies-and-pd-1-blockade-enhances-the-antitumor-potency-of-t-cells
#10
Chien-Hsing Chang, Yang Wang, Rongxiu Li, Diane L Rossi, Donglin Liu, Edmund A Rossi, Thomas M Cardillo, David M Goldenberg
The DOCK-AND-LOCK (DNL®) method is a platform technology that combines recombinant engineering and site-specific conjugation to create multispecific, multivalent antibodies of defined composition with retained bioactivity. We have applied DNL® to generate a novel class of trivalent bispecific antibodies (bsAbs), each comprising an anti-CD3 scFv covalently conjugated to a stabilized dimer of different anti-tumor Fabs. Here we report the further characterization of two such constructs, (E1)-3s and (14)-3s, which activate T cells and target Trop-2- and CEACAM5-expressing cancer cells, respectively...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28815913/metastatic-triple-negative-breast-cancer-optimizing-treatment-options-new-and-emerging-targeted-therapies
#11
REVIEW
Parham Khosravi-Shahi, Luis Cabezón-Gutiérrez, Sara Custodio-Cabello
Triple negative breast cancer (TNBC) is a heterogeneous disease, not only on the molecular level, but also on the pathologic and clinical levels. It also has a distinct epidemiology. TNBCs are frequently of high histologic grade, typically more aggressive and difficult to treat than hormone receptor-positive tumors, and they are associated with a higher risk of early relapse with visceral metastasis after surgery, chemotherapy and/or radiotherapy. The lack of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression precludes the use of targeted therapies in advanced stages, and the only approved systemic treatment option is chemotherapy with or without bevacizumab...
August 16, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28801472/breast-cancer-immunotherapy-facts-and-hopes
#12
Leisha A Emens
Immunotherapy is revolutionizing the management of multiple solid tumors, and early data have revealed the clinical activity of PD-1/PD-L1 antagonists in small numbers of metastatic breast cancer patients. Clinical activity appears more likely if the tumor is triple negative, PD-L1+, and/or harbors higher levels of TILs. Responses to atezolizumab and pembrolizumab appear to be durable in metastatic triple negative breast cancer (TNBC), suggesting these agents may transform the lives of responding patients. Current clinical efforts are focused on developing immunotherapy combinations that convert non-responders to responders, deepen those responses that do occur, and surmount acquired resistance to immunotherapy...
August 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28799073/immunotherapy-in-breast-cancer-the-emerging-role-of-pd-1-and-pd-l1
#13
REVIEW
François Bertucci, Anthony Gonçalves
PURPOSE OF REVIEW: The purpose of the review is to summarize the data regarding PD-L1 expression in breast cancer and the results of first clinical trials with PD-1 or PD-L1 inhibitors in patients with metastatic breast cancer. RECENT FINDINGS: PD-L1 expression is heterogeneous across primary breast cancers, and is generally associated with the presence of tumor-infiltrating lymphocytes and the presence of poor-prognosis features such as high grade, and aggressive molecular subtypes (triple-negative (TN), basal, HER2-enriched)...
August 10, 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28761741/tumour-infiltrating-lymphocytes-are-correlated-with-higher-expression-levels-of-pd-1-and-pd-l1-in-early-breast-cancer
#14
Atsuko Kitano, Makiko Ono, Masayuki Yoshida, Emi Noguchi, Akihiko Shimomura, Tatsunori Shimoi, Makoto Kodaira, Mayu Yunokawa, Kan Yonemori, Chikako Shimizu, Takayuki Kinoshita, Yasuhiro Fujiwara, Hitoshi Tsuda, Kenji Tamura
BACKGROUND: The presence of tumour-infiltrating lymphocytes (TILs) is a favourable prognostic factor in patients with early breast cancer. Programmed cell death-1 (PD-1) and its ligand PD-L1 are associated with a variety of adverse features. The purpose of this study was to clarify the relationships between TILs, PD-1 and PD-L1 as well as their prognostic implications in early breast cancer. METHODS: We investigated 180 patients with breast cancer who received neoadjuvant chemotherapy and underwent subsequent surgery for stage II-III invasive breast carcinoma between 1999 and 2007...
2017: ESMO Open
https://www.readbyqxmd.com/read/28752839/development-and-validation-of-a-novel-clinical-fluorescence-in-situ-hybridization-assay-to-detect-jak2-and-pd-l1-amplification-a-fluorescence-in-situ-hybridization-assay-for-jak2-and-pd-l1-amplification
#15
Meixuan Chen, Mariacarla Andreozzi, Barbara Pockaj, Michael T Barrett, Idris Tolgay Ocal, Ann E McCullough, Maria E Linnaus, James M Chang, Jennifer H Yearley, Lakshmanan Annamalai, Karen S Anderson
The amplification of chromosome 9p24.1 encoding PD-L1, PD-L2, and JAK2 has been reported in multiple types of cancer and is associated with poor outcome, upregulation of PD-L1, and activation of the JAK/STAT pathway. We have developed a novel fluorescence in situ hybridization assay which combines 3 probes mapping to 9p24.1 with a commercial chromosome 9 centromere (CEN9) probe for detection of the JAK2/9p24.1 amplification. JAK2 fluorescence in situ hybridization was compared with array-based comparative genomic hybridization in 34 samples of triple negative breast cancer tumor...
July 28, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28733529/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#16
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28731046/pd-l1-expression-and-the-immune-microenvironment-in-primary-invasive-lobular-carcinomas-of-the-breast
#17
Elizabeth D Thompson, Janis M Taube, Rebecca J Asch-Kendrick, Aleksandra Ogurtsova, Haiying Xu, Rajni Sharma, Alan Meeker, Pedram Argani, Leisha A Emens, Ashley Cimino-Mathews
Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (<5%); 2+ (5-10%); 3+ (10-15%); or 4+ (>50%)...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28721684/pharmacokinetics-microscale-distribution-and-dosimetry-of-alpha-emitter-labeled-anti-pd-l1-antibodies-in-an-immune-competent-transgenic-breast-cancer-model
#18
Jessie R Nedrow, Anders Josefsson, Sunju Park, Tom Bäck, Robert F Hobbs, Cory Brayton, Frank Bruchertseifer, Alfred Morgenstern, George Sgouros
BACKGROUND: Studies combining immune checkpoint inhibitors with external beam radiation have shown a therapeutic advantage over each modality alone. The purpose of these works is to evaluate the potential of targeted delivery of high LET radiation to the tumor microenvironment via an immune checkpoint inhibitor. METHODS: The impact of protein concentration on the distribution of (111)In-DTPA-anti-PD-L1-BC, an (111)In-antibody conjugate targeted to PD-L1, was evaluated in an immunocompetent mouse model of breast cancer...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28697066/viral-induced-modulation-of-multiple-checkpoint-proteins-in-cancers
#19
Gerard J Nuovo, Virginia A Folcik, Cynthia Magro
Therapy with checkpoint inhibitors represents a major advance in cancer treatment. The purpose of this study was to examine the expression patterns of the checkpoint proteins programmed death ligand 1 (PD L1), PD L2, indoleamine 2,3-dioxygenase 1 (IDO1), and cytotoxic T-lymphocyte antigen 4 (CTLA4) in cancers including those associated with viral infections. Normal, noninflamed tissues rarely express checkpoint proteins with exceptions including the placenta and stomach. Expression of PD L1 was noted in 30%, PD L2 in 18%, IDO1 in 13%, and CTLA4 in 14% of 333 nonviral malignancies including endometrial, ovarian, lung, and breast cancers...
July 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28680745/vaccination-targeting-human-her3-alters-the-phenotype-of-infiltrating-t-cells-and-responses-to-immune-checkpoint-inhibition
#20
Takuya Osada, Michael A Morse, Amy Hobeika, Marcio A Diniz, William R Gwin, Zachary Hartman, Junping Wei, Hongtao Guo, Xiao-Yi Yang, Cong-Xiao Liu, Kensuke Kaneko, Gloria Broadwater, H Kim Lyerly
Expression of human epidermal growth factor family member 3 (HER3), a critical heterodimerization partner with EGFR and HER2, promotes more aggressive biology in breast and other epithelial malignancies. As such, inhibiting HER3 could have broad applicability to the treatment of EGFR- and HER2-driven tumors. Although lack of a functional kinase domain limits the use of receptor tyrosine kinase inhibitors, HER3 contains antigenic targets for T cells and antibodies. Using novel human HER3 transgenic mouse models of breast cancer, we demonstrate that immunization with recombinant adenoviral vectors encoding full length human HER3 (Ad-HER3-FL) induces HER3-specific T cells and antibodies, alters the T cell infiltrate in tumors, and influences responses to immune checkpoint inhibitions...
2017: Oncoimmunology
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