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Tumor infiltrating lymphocyte breast

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https://www.readbyqxmd.com/read/28289852/tumor-infiltrating-lymphocytes-and-molecular-response-after-neoadjuvant-therapy-for-hr-her2-%C3%A2-breast-cancer-results-from-two-prospective-trials
#1
M V Dieci, A Frassoldati, D Generali, G Bisagni, F Piacentini, L Cavanna, K Cagossi, F Puglisi, A Michelotti, R Berardi, G Banna, A Goubar, G Ficarra, G Griguolo, Pierfranco Conte, V Guarneri
PURPOSE: The aim was to evaluate the role of tumor-infiltrating lymphocytes (TIL) in predicting molecular response after preoperative endocrine or cytotoxic treatment for HR+/HER2- patients who do not achieve a pathological complete response. METHODS: Stromal (Str) TIL were centrally evaluated on samples from diagnostic core-biopsies of HR+/HER2- patients included in two prospective randomized trials: the LETLOB trial (neoadjuvant endocrine-based treatment) and the GIOB trial (neoadjuvant chemotherapy-based treatment)...
March 13, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28285968/histologic-factors-predicting-invasion-in-patients-with-ductal-carcinoma-in-situ-dcis-in-the-preoperative-core-biopsy
#2
Areej M Al Nemer
BACKGROUND: It is desirable to decrease the underestimation rate of invasion in cases diagnosed as ductal carcinoma in situ (DCIS) in breast core needle biopsy (CNB) in order to determine the appropriate candidates for axillary staging. The objective of this study is to identify the predictors of invasion in histology. METHODS AND RESULTS: Consecutive 92 CNB's were retrospectively evaluated. The upstaging rate was 47.8% after surgery. Among all the evaluated parameters, high nuclear grade, single architectural pattern, marked periductal lymphocytic infiltration, partial myoepithelial loss and the presence of foci suspicious of microinvasion were the significant predictors of invasion (two tailed p values 0...
February 24, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28281220/the-multifaceted-roles-of-b-cells-in-solid-tumors-emerging-treatment-opportunities
#3
Nicole J Flynn, Rajasekharan Somasundaram, Kimberly M Arnold, Jennifer Sims-Mourtada
The influence of tumor infiltrating lymphocytes on tumor growth and response to therapy is becoming increasingly apparent. While much work has focused on the role of T cell responses in anti-tumor immunity, the role of B cells in solid tumors is much less understood. Tumor infiltrating B cells have been found in a variety of solid tumors, including breast, ovarian, prostate, melanoma, and colorectal cancer. The function of B cells in solid tumors is controversial, with many studies reporting a pro-tumor effect, while other studies demonstrate a role for B cells in the anti-tumor immune response...
March 9, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28278438/diagnosis-of-autoimmune-pancreatitis-with-cholesterol-granuloma-mimicking-intraductal-papillary-mucinous-carcinoma-a-case-report
#4
Yusuke Takahashi, Naoyuki Yokoyama, Daisuke Sato, Tetsuya Otani, Koko Mitsuma, Hideki Hashidate
INTRODUCTION: Pancreatic cysts are often observed incidentally on abdominal computed tomography (CT). For cysts involving intracystic nodules, malignant neoplasms such as intraductal papillary-mucinous carcinoma (IPMC) should be suspected. In contrast, cholesterol granuloma (CG) rarely occurs in the pancreas, and CG-associated autoimmune pancreatitis (AIP) has not yet been reported. To our knowledge, this is the first reported case of AIP with CG mimicking IPMC. PRESENTATION OF CASE: A 56-year-old woman underwent abdominal CT for preoperative breast cancer screening...
March 1, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28270498/a-randomized-phase-ii-neoadjuvant-study-of-cisplatin-paclitaxel-with-or-without-everolimus-in-patients-with-stage-ii-iii-triple-negative-breast-cancer-tnbc
#5
Bojana Jovanovic, Ingrid A Mayer, Erica L Mayer, Vandana G Abramson, Aditya Bardia, Melinda Sanders, Maria G Kuba, Monica Valeria Estrada, J Scott Beeler, Timothy M Shaver, Kimberly N Johnson, Violeta Sanchez, Jennifer M Rosenbluth, Patrick M Dillon, Andres Forrero-Torres, Jenny C Chang, Ingrid Meszoely, Ana Grau, Brian D Lehmann, Yu Shyr, Quanhu Sheng, Sheau-Chiann Chen, Carlos L Arteaga, Jennifer A Pietenpol
PURPOSE: Due to inherent disease heterogeneity, targeted therapies have eluded TNBC, and biomarkers predictive of treatment response have not yet been identified. This study was designed to determine if the mTOR inhibitor everolimus with cisplatin and paclitaxel would provide synergistic anti-tumor effects in TNBC. EXPERIMENTAL DESIGN: Stage II/III patients with TNBC were enrolled in a randomized phase II trial of preoperative weekly cisplatin, paclitaxel and daily everolimus or placebo for 12 weeks, until definitive surgery...
March 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28264810/promoter-methylation-modulates-indoleamine-2-3-dioxygenase-1-induction-by-activated-t-cells-in-human-breast-cancers
#6
Satish K Noonepalle, Franklin Gu, Eun-Joon Lee, Jeong-Hyeon Choi, Qimei Han, Jaejik Kim, Maria Ouzounova, Austin Y Shull, Lirong Pei, Pei-Yin Hsu, Ravindra Kohle, Fang Shi, Jiseok Choi, Katie Chiou, Tim H M Huang, Hasan Korkaya, Libin Deng, Hong-Bo Xin, Shuang Huang, Muthusamy Thangaraju, Arun Sreekumar, Stefan Ambs, Shou-Ching Tang, David H Munn, Huidong Shi
Triple-negative breast cancer (TNBC) cells are modulated in reaction to tumor-infiltrating lymphocytes. However, their specific responses to this immune pressure are unknown. In order to address this question, we first used mRNA sequencing to compare the immunophenotype of the TNBC cell line MDA-MB-231 and the luminal breast cancer cell line MCF7 after both were cocultured with activated human T cells. Despite similarities in the cytokine-induced immune signatures of the two cell lines, MDA-MD-231 cells were able to transcribe more IDO1 than MCF7 cells...
March 6, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28254787/serine-proteases-enhance-immunogenic-antigen-presentation-on-lung-cancer-cells
#7
Haley L Peters, Satyendra C Tripathi, Celine Kerros, Hiroyuki Katayama, Haven R Garber, Lisa S St John, Lorenzo Federico, Ismail M Meraz, Jack A Roth, Boris Sepesi, Mourad Majidi, Kathryn Ruisaard, Karen Clise-Dwyer, Jason Roszik, Don L Gibbons, John Heymach, Stephen G Swisher, Chantale Bernantchez, Gheath Alatrash, Samir M Hanash, Jeffrey J Molldrem
Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer in patients; however, the antigenic targets of these re-invigorated T cells remain poorly defined. Lung cancer tumors contain tumor-associated macrophages (TAM) and neutrophils, which release the serine proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor microenvironment. NE and P3 shape the antitumor adaptive immune response in breast cancer and melanoma. In this report, we demonstrate that lung cancer cells cross-presented the tumor-associated antigen PR1, derived from NE and P3...
March 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28254786/clinical-impact-of-tumor-dna-repair-expression-and-t-cell-infiltration-in-breast-cancers
#8
Andrew R Green, Mohammed A Aleskandarany, Reem Ali, Eleanor Grace Hodgson, Suha Atabani, Karen De Souza, Emad Rakha, Ian O Ellis, Srinivasan Madhusudan
Impaired DNA repair drives mutagenicity, which increases neoantigen load and immunogenicity. We investigated the expression of proteins involved in the DNA damage response (ATM, Chk2), double-strand break repair (BRCA1, BLM, WRN, RECQL4, RECQL5, TOPO2A, DNA-PKcs, Ku70/Ku80), nucleotide excision repair (ERCC1), base excision repair (XRCC1, pol β, FEN1, PARP1), and immune responses (CD8, PD-1, PD-L1, FOXP3) in 1269 breast cancers and validated our findings in an independent estrogen receptor (ER)- cohort (n = 279)...
March 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28230773/programmed-death-ligand-1-pd-l1-tumor-expression-is-associated-with-a-better-prognosis-and-diabetic-disease-in-triple-negative-breast-cancer-patients
#9
Gerardo Botti, Francesca Collina, Giosuè Scognamiglio, Federica Rao, Valentina Peluso, Rossella De Cecio, Michela Piezzo, Gabriella Landi, Michelino De Laurentiis, Monica Cantile, Maurizio Di Bonito
Triple Negative Breast Cancers (TNBC) subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1) is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28206673/the-immune-system-as-a-new-possible-cell-target-for-afp-464-in-a-spontaneous-mammary-cancer-mouse-model
#10
Mariana A Callero, Cristina E Rodriguez, Aldana Sólimo, Elisa Bal de Kier Joffé, Andrea I Loaiza Perez
Aminoflavone (AFP 464, NSC 710464), an antitumor agent which recently entered phase II clinical trials, acts against estrogen-positive breast cancer (ER +). AFP 464, which has a unique mechanism of action by activating aryl hydrocarbon receptor (AhR) signaling pathway, decreased tumor size and growth rate in the estrogen dependent, Tamoxifen-sensitive spontaneous M05 mouse model. Considering that AhR has recently emerged as a physiological regulator of the innate and adaptive immune responses, we investigated whether AFP 464 modulates the immune response in our mouse model...
February 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28197375/tumor-infiltrating-lymphocyte-composition-organization-and-pd-1-pd-l1-expression-are-linked-in-breast-cancer
#11
Laurence Buisseret, Soizic Garaud, Alexandre de Wind, Gert Van den Eynden, Anais Boisson, Cinzia Solinas, Chunyan Gu-Trantien, Céline Naveaux, Jean-Nicolas Lodewyckx, Hugues Duvillier, Ligia Craciun, Isabelle Veys, Denis Larsimont, Martine Piccart-Gebhart, John Stagg, Christos Sotiriou, Karen Willard-Gallo
The clinical relevance of tumor-infiltrating lymphocytes (TIL) in breast cancer (BC) has been clearly established by their demonstrated correlation with long-term positive outcomes. Nevertheless, the relationship between protective immunity, observed in some patients, and critical features of the infiltrate remains unresolved. This study examined TIL density, composition and organization together with PD-1 and PD-L1 expression in freshly collected and paraffin-embedded tissues from 125 patients with invasive primary BC...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28187033/prognostic-significance-of-stromal-versus-intratumoral-infiltrating-lymphocytes-in-different-subtypes-of-breast-cancer-treated-with-cytotoxic-neoadjuvant-chemotherapy
#12
Thaer Khoury, Vidya Nagrale, Mateusz Opyrchal, Xuan Peng, Dan Wang, Song Yao
BACKGROUND: The aim of the study was to investigate if there were differences in associations of stromal versus intratumoral tumor infiltrating lymphocytes (TILs) with pathology complete response (pCR) among breast cancer (BC) subtypes treated with neoadjuvant therapy. MATERIALS AND METHODS: The hematoxylin and eosin slides of BC-core biopsy consecutive cases (n=331) were reviewed from a single institution between 2000 and 2014. TIL-stroma (TIL-str) was scored from 0% to 100%...
February 9, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28185053/glutaminase-expression-is-a-poor-prognostic-factor-in-node-positive-triple-negative-breast-cancer-patients-with-a-high-level-of-tumor-infiltrating-lymphocytes
#13
Joo Young Kim, Sun-Hee Heo, Seul Ki Choi, In Hye Song, In Ah Park, Young-Ae Kim, Hye Seon Park, Suk Young Park, Won Seon Bang, Gyungyub Gong, Hee Jin Lee
Glutamine metabolism is emerging as one aspect of dysregulated metabolism of tumors. Triple-negative breast cancer (TNBC) cells are glutamine dependent, whereas luminal-type cells tend to be glutamine independent. Therefore, TNBC patients might benefit from therapies targeting glutamine metabolism. To investigate the clinical significance of glutamine metabolism, we examined expression and prognostic significance of glutaminase in tumor cells and tumor-infiltrating lymphocytes (TILs) in TNBC. We retrieved 658 surgically resected TNBCs and analyzed glutaminase expression in tumor cells and TILs by immunohistochemical staining...
February 9, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28178752/prognostic-significance-of-cd9-expression-differs-between-tumor-cells-and-stromal-immune-cells-and-depends-on-the-molecular-subtype-of-the-invasive-breast-carcinoma
#14
Hee Jung Kwon, Jung Eun Choi, Su Hwan Kang, Youlim Son, Young Kyung Bae
AIMS: CD9, a tetraspanin transmembrane protein, modulates cell motility, migration, and proliferation. We investigated the prognostic significance of CD9 expression in patients with invasive breast carcinoma (IBC). METHODS AND RESULTS: CD9 expression was evaluated in tissue microarrays of 1349 IBC samples via immunohistochemistry. CD9 expression in tumor cells (T-CD9) and stromal immune cells (S-CD9) were analyzed separately. T-CD9 expression was observed in 732 (54...
February 8, 2017: Histopathology
https://www.readbyqxmd.com/read/28167507/parp-inhibitor-upregulates-pd-l1-expression-and-enhances-cancer-associated-immunosuppression
#15
Shiping Jiao, Weiya Xia, Hirohito Yamaguchi, Yongkun Wei, Mei-Kuang Chen, Jung-Mao Hsu, Jennifer L Hsu, Wen-Hsuan Yu, Yi Du, Heng-Huan Lee, Chia-Wei Li, Chao-Kai Chou, Seung-Oe Lim, Shih-Shin Chang, Jennifer K Litton, Banu Arun, Gabriel N Hortobagyi, Mien-Chie Hung
PURPOSE: To explore whether a crosstalk exists between PARP inhibition and PD-L1/ PD-1 immune checkpoint axis, and determine if blockade of PD-L1/ PD-1 potentiates PARP inhibitor (PARPi) in tumor suppression. EXPERIMENTAL DESIGN: Breast cancer cell lines, xenograft tumors and syngeneic tumors treated with PARPi were assessed for PD-L1 expression by immunoblotting, immunohistochemistry and FACS analyses. The phospho-kinase antibody array screen was used to explore the underlying mechanism of PARPi-induced PD-L1 upregulation...
February 6, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28166544/use-of-tumor-infiltrating-lymphocytes-tils-to-predict-the-treatment-response-to-eribulin-chemotherapy-in-breast-cancer
#16
Shinichiro Kashiwagi, Yuka Asano, Wataru Goto, Koji Takada, Katsuyuki Takahashi, Satoru Noda, Tsutomu Takashima, Naoyoshi Onoda, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: Eribulin mesylate (eribulin) is currently indicated for treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress epithelial-mesenchymal transition (EMT) of cancer cells. On the other hand, Tumor-infiltrating lymphocytes (TILs), which are considered indicators of immune response monitoring, have been reported as prognostic factors and predictors of therapeutic efficacy. We thought that eribulin, which has an EMT-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with TILs as a marker...
2017: PloS One
https://www.readbyqxmd.com/read/28162837/immunotherapy-in-breast-cancer-an-introduction
#17
Mary L Disis, Sasha E Stanton
The field of breast cancer immunology has progressed tremendously over the last decade. Twenty years ago immunotherapy was not considered for the treatment of breast cancers because breast cancer was not considered immunogenic. Today we know that most patients with breast cancer have some evidence of an adaptive immune response against their tumors, detectable either in the peripheral blood or in the tumor. Moreover, immunity to breast cancer begins at the earliest stages of the disease, in some patients prior to diagnosis...
February 3, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28159748/estradiol-promotes-breast-cancer-cell-migration-via-recruitment-and-activation-of-neutrophils
#18
Gabriela Vazquez Rodriguez, Annelie Abrahamsson, Lasse Dahl Ejby Jensen, Charlotta Dabrosin
Estradiol (E2) plays a key role in breast cancer progression. Most breast cancer recurrences express the estrogen receptor (ER), but nearly 50% of patients are resistant to antiestrogen therapy. Novel therapeutic targets of ER-positive breast cancers are needed. Protumoral neutrophils expressing the lymphocyte function-associated antigen 1 (LFA-1) integrin may mediate cancer metastasis, and TGFβ1 is the major chemoattractant for neutrophils. The role of E2 in neutrophil-ER(+) breast cancer cell interactions is unknown...
February 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28159402/-evaluation-of-tumor-infiltrating-lymphocytes-in-breast-cancer-how-to-use-the-2014%C3%A2-international-guidelines
#19
Natacha Joyon, Manal Kordahi, Cécile Blanc-Fournier, Magali Lacroix-Triki
With the major development of immunotherapies, evaluation of the immune response associated to cancer has become the new challenge for pathologists. In breast cancer, this perspective has been notably anticipated by the recent publication, in 2014, of international guidelines for assessment of tumor-infiltrating lymphocytes (TILs), on routine haematoxylin-eosin stains. This technical article aims at reviewing the main key points and different steps in evaluation of tumor-infiltrating lymphocytes, in order to allow an easy implementation of this putative biomarker in routine practice...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28153508/tumor-infiltrating-lymphocytes-are-significantly-associated-with-better-overall-survival-and-disease-free-survival-in-triple-negative-but-not-estrogen-receptor-positive-breast-cancers
#20
Uma Krishnamurti, Ceyda Sonmez Wetherilt, Jing Yang, Limin Peng, Xiaoxian Li
Correlation between tumor-infiltrating lymphocytes (TILs) and complete pathological response (pCR) in breast cancers in neoadjuvant settings has been reported. In this study, we analyzed the association between TILs and diagnostic and prognostic parameters in estrogen receptor positive (ER+) and triple-negative breast cancer (TNBC) without neoadjuvant treatments. Three hundred and forty-four (344) patients who underwent mastectomy for breast cancer (187 ER+ and 157 TNBC) without neoadjuvant treatments were evaluated...
January 30, 2017: Human Pathology
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