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Tumor infiltrating lymphocyte breast

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https://www.readbyqxmd.com/read/29045543/a-predictive-model-of-pathological-response-based-on-tumor-cellularity-and-tumor-infiltrating-lymphocytes-celtil-in-her2-positive-breast-cancer-treated-with-chemo-free-dual-her2-blockade
#1
P Nuciforo, T Pascual, J Cortés, A Llombart-Cussac, R Fasani, L Paré, M Oliveira, P Galvan, N Martínez, B Bermejo, M Vidal, S Pernas, R López, M Muñoz, I Garau, L Manso, J Alarcón, E Martínez, V Rodrik-Outmezguine, J C Brase, P Villagrasa, A Prat, E Holgado
Background: The presence of stromal tumor-infiltrating lymphocytes (TILs) is associated with increased pathological complete response (pCR) and improved outcomes in HER2-positive early breast cancer (BC) treated with anti-HER2-based chemotherapy. In the absence of chemotherapy, the association of TILs with pCR following anti-HER2 therapy-only is largely unknown. Patients and methods: The PAMELA neoadjuvant trial treated 151 women with HER2-positive BC with lapatinib and trastuzumab (and hormonal therapy if hormone receptor [HR]-positive) for 18 weeks...
October 12, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045526/lag-3-tumor-infiltrating-lymphocytes-in-breast-cancer-clinical-correlates-and-association-with-pd-1-pd-l1-tumors
#2
S Burugu, D Gao, S Leung, S K Chia, T O Nielsen
BACKGROUND: Novel immune checkpoint blockade strategies are being evaluated in clinical trials and include targeting the lymphocyte activation gene 3 (LAG-3) checkpoint, alone or in combination with PD-1/PD-L1 blockade. We investigated LAG-3 expression and its prognostic value in a large series of breast cancer patients, and correlated LAG-3 expression with key biomarkers including PD-1 and PD-L1. EXPERIMENTAL DESIGN: LAG-3 expression was evaluated by immunohistochemistry (IHC) on two tissue microarray series incorporating 4322 breast cancer primary excision specimens (N=330 in the training and N= 3,992 in the validation set) linked to detailed clinico-pathological, biomarker and long term clinical outcome data...
September 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29037255/objective-measurement-and-clinical-significance-of-ido1-protein-in-hormone-receptor-positive-breast-cancer
#3
Daniel E Carvajal-Hausdorf, Nikita Mani, Vamsidhar Velcheti, Kurt A Schalper, David L Rimm
BACKGROUND: Immunostimulatory therapies targeting immune-suppressive pathways produce durable responses in advanced solid tumors. Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting oxidoreductase that catalyzes the degradation of tryptophan to kynurenine. IDO induces immune tolerance by downregulating CD8+ and effector CD4+ T cell responses. IDO1, the most active isoform, is expressed in diverse tumor types and can be targeted using small molecule inhibitors. We used an objective, in situ assay to measure IDO1 in a collection of hormone receptor-positive breast cancers (HR+ BC)...
October 17, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29026362/inflammatory-myofibroblastic-tumor-of-the-breast-mimicking-malignancy-in-an-elderly-male
#4
Fouzia Siraj, Manveen Kaur, Varsha Dalal, Jain Sonam
BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare, distinctive lesion composed of a proliferation of myofibroblastic spindle cells accompanied by an inflammatory infiltrate. It was first described in the lung, but its occurrence at various extrapulmonary sites has also been reported. The literature mentions only a handful of cases of IMT in the breast and only 1 case in the male breast. We report the second case of IMT in the male breast. CASE REPORT: A 60-year-old male presented with a large, lobulated lump in the left breast that had progressively increased in size during the past year...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29024776/update-on-tumor-infiltrating-lymphocytes-tils-in-breast-cancer-including-recommendations-to-assess-tils-in-residual-disease-after-neoadjuvant-therapy-and-in-carcinoma-in-situ-a-report-of-the-international-immuno-oncology-biomarker-working-group-on-breast-cancer
#5
REVIEW
Maria Vittoria Dieci, Nina Radosevic-Robin, Susan Fineberg, Gert van den Eynden, Nils Ternes, Frederique Penault-Llorca, Giancarlo Pruneri, Timothy M D'Alfonso, Sandra Demaria, Carlos Castaneda, Joselyn Sanchez, Sunil Badve, Stefan Michiels, Veerle Bossuyt, Federico Rojo, Baljit Singh, Torsten Nielsen, Giuseppe Viale, Seong-Rim Kim, Stephen Hewitt, Stephan Wienert, Sybille Loibl, David Rimm, Fraser Symmans, Carsten Denkert, Sylvia Adams, Sherene Loi, Roberto Salgado
Morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer is gaining momentum as evidence strengthens the clinical relevance of this immunological biomarker. TILs in the post-neoadjuvant residual disease setting are acquiring increasing importance as a stratifying marker in clinical trials, considering the raising interest on immunotherapeutic strategies after neoadjuvant chemotherapy. TILs in ductal carcinoma in situ, with or without invasive carcinoma, represent an emerging area of clinical breast cancer research...
October 9, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28993275/the-cd4-cd8-ratio-of-tumor-infiltrating-lymphocytes-at-the-tumor-host-interface-has-prognostic-value-in-triple-negative-breast-cancer
#6
Kai Wang, Tiansheng Shen, Gene P Siegal, Shi Wei
Compelling evidence has demonstrated the prognostic value of tumor-infiltrating lymphocytes (TILs), especially in triple-negative breast cancer (TNBC). However, only a limited number of studies to investigate the importance of the subsets of T cells in TILs has been carried out, less so the significance of the location of these TILs. In this study, we explored in a cohort of 42 consecutive TNBC cases the prognostic significance of TIL subsets at the tumor-host interface (within one high power field [0.5 μm] of the invasive front) and compared them to TILs within the intratumoral stroma...
October 6, 2017: Human Pathology
https://www.readbyqxmd.com/read/28986972/invasive-breast-carcinomas-with-atm-gene-variants-of-uncertain-significance-share-distinct-histopathologic-features
#7
Ahmed A Abdulrahman, Rebecca C Heintzelman, Melanie Corbman, Fernando U Garcia
The increasing availability of next-generation sequencing for clinical research dramatically improved our understanding of breast cancer genetics and resulted in detection of new mutation variants. Cancer risk data relating to some of these variants are insufficient, prompting the designation of variants of uncertain significance (VUS). The histopathologic characteristics of these variants have not been previously described. We propose to depict these characteristics and determine if invasive carcinomas with similar VUS genes share similar histomorphologic features...
October 7, 2017: Breast Journal
https://www.readbyqxmd.com/read/28984302/composite-analysis-of-immunological-and-metabolic-markers-defines-novel-subtypes-of-triple-negative-breast-cancer
#8
Thomas A Adams, Paris J Vail, Amanda Ruiz, Mehri Mollaee, Peter A McCue, Erik S Knudsen, Agnieszka K Witkiewicz
Cancer biology is influenced by the tumor microenvironment, which impacts disease prognosis and therapeutic interventions. The inter-relationship of tumor-infiltrating lymphocytes, immune response regulators, and a glycolytic tumor environment was evaluated in a cohort of 183 largely consecutive patients with triple negative breast cancer diagnosis. High levels of tumor-infiltrating lymphocytes were associated with improved survival of triple negative breast cancer cases. However, elevated levels of PD-L1, CD163, and FOXP3 were individually associated with significantly decreased overall survival...
October 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28982879/using-tils-to-predict-therapeutic-effect-of-chemotherapy-pertuzumab-trastuzumab-docetaxel-on-her2-positive-breast-cancer
#9
Shinichiro Kashiwagi, Yuka Asano, Wataru Goto, Koji Takada, Katsuyuki Takahashi, Takaharu Hatano, Tsutomu Takashima, Shuhei Tomita, Hisashi Motomura, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND/AIM: Recently, reports of the clinical implications of tumor-infiltrating lymphocytes (TILs) in breast cancer treatment have increased. We evaluated that chemotherapy with a TPD regimen (trastuzumab, pertuzumab, docetaxel) against HER2-positive breast cancer, using TILs as indicators. PATIENTS AND METHODS: The subjects were 24 patients who had received TPD-chemotherapy. A semi-quantitative evaluation of lymphocytes invading the stroma in needle biopsy specimens prior to treatment as TILs was conducted, after which, sensitivity to chemotherapy and patient prognosis were evaluated...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28979132/impact-of-the-tumor-microenvironment-on-tumor-infiltrating-lymphocytes-focus-on-breast-cancer
#10
REVIEW
Ivan J Cohen, Ronald Blasberg
Immunotherapy is revolutionizing cancer care across disciplines. The original success of immune checkpoint blockade in melanoma has already been translated to Food and Drug Administration-approved therapies in a number of other cancers, and a large number of clinical trials are underway in many other disease types, including breast cancer. Here, we review the basic requirements for a successful antitumor immune response, with a focus on the metabolic and physical barriers encountered by lymphocytes entering breast tumors...
2017: Breast Cancer: Basic and Clinical Research
https://www.readbyqxmd.com/read/28977923/integrated-analysis-of-somatic-mutations-and-immune-microenvironment-of-multiple-regions-in-breast-cancers
#11
Taigo Kato, Jae-Hyun Park, Kazuma Kiyotani, Yuji Ikeda, Yasuo Miyoshi, Yusuke Nakamura
Next-generation sequencing technology enables us to analyze the complexity of intra- and inter-tumoral heterogeneity, which may influence to prognosis of cancer patients. In this study, we collected surgically-resected tumor tissues from five breast cancer patients and characterized three different portions of individual tumors through somatic mutation analysis by whole exome sequencing, T cell receptor beta (TCRB) repertoire analysis of tumor-infiltrating lymphocytes (TILs), and the expression analysis of immune-related genes at 15 different sites...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28946899/erratum-to-effect-of-neoadjuvant-chemotherapy-on-tumor-infiltrating-lymphocytes-and-pd-l1-expression-in-breast-cancer-and-its-clinical-significance
#12
Vasiliki Pelekanou, Daniel E Carvajal-Hausdorf, Mehmet Altan, Brad Wasserman, Cristobal Carvajal-Hausdorf, Hallie Wimberly, Jason Brown, Donald Lannin, Lajos Pusztai, David L Rimm
No abstract text is available yet for this article.
September 25, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28937963/ki67-and-lymphocytes-in-the-pretherapeutic-core-biopsy-of-primary-invasive-breast-cancer-positive-markers-of-therapy-response-prediction-and-superior-survival
#13
REVIEW
Claus M Schlotter, Lothar Tietze, Ulf Vogt, Carlos Villena Heinsen, Antje Hahn
Background Core needle biopsy plays a crucial role as diagnostic tool for BC. Both Ki67 and likely tumor-infiltrating lymphocytes (TILs) in the near future are determining the kind of systemic therapy. The role of TILs in BC is still an issue for clinical research, albeit preliminary results of neoadjuvant and adjuvant clinical studies already now highlight the crucial impact of TILs on therapy response and survival. Methods Evaluation of related publications (pubmed) and meeting abstracts (ASCO, SABCS). Results The monoclonal antibody Ki67 recognizing a nuclear antigene in proliferating cells is a positive marker of therapy response and superior survival...
September 22, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28936553/significance-of-evaluating-tumor-infiltrating-lymphocytes-tils-and-programmed-cell-death-ligand-1-pd-l1-expression-in-breast-cancer
#14
REVIEW
Sasagu Kurozumi, Takaaki Fujii, Hiroshi Matsumoto, Kenichi Inoue, Masafumi Kurosumi, Jun Horiguchi, Hiroyuki Kuwano
The immune system affects all phases of tumor growth from initiation to progression and dissemination. Tumor-infiltrating lymphocytes (TILs) are mononuclear immune cells that infiltrate tumor tissue. Several retrospective studies have suggested the potential of TILs as a prognostic as well as predictive factor of chemotherapy in some breast cancers. On the other hand, programmed cell death protein-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) eliminate T cell activation in various types of cancers. Prospective trials to evaluate the efficacy of antibody agents to PD-1 and PD-L1 are ongoing in patients with breast cancer...
September 21, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28931370/association-between-tumour-infiltrating-lymphocytes-histotype-and-clinical-outcome-in-epithelial-ovarian-cancer
#15
Fiona R James, Mercedes Jiminez-Linan, Jennifer Alsop, Marie Mack, Honglin Song, James D Brenton, Paul D P Pharoah, H Raza Ali
BACKGROUND: There is evidence that some ovarian tumours evoke an immune response, which can be assessed by tumour infiltrating lymphocytes (TILs). To facilitate adoption of TILs as a clinical biomarker, a standardised method for their H&E visual evaluation has been validated in breast cancer. METHODS: We sought to investigate the prognostic significance of TILs in a study of 953 invasive epithelial ovarian cancer tumour samples, both primary and metastatic, from 707 patients from the prospective population-based SEARCH study...
September 20, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28928458/agonist-immunotherapy-restores-t-cell-function-following-mek-inhibition-improving-efficacy-in-breast-cancer
#16
Sathana Dushyanthen, Zhi Ling Teo, Franco Caramia, Peter Savas, Christopher P Mintoff, Balaji Virassamy, Melissa A Henderson, Stephen J Luen, Mariam Mansour, Michael H Kershaw, Joseph A Trapani, Paul J Neeson, Roberto Salgado, Grant A McArthur, Justin M Balko, Paul A Beavis, Phillip K Darcy, Sherene Loi
The presence of tumor-infiltrating lymphocytes in triple-negative breast cancers is correlated with improved outcomes. Ras/MAPK pathway activation is associated with significantly lower levels of tumor-infiltrating lymphocytes in triple-negative breast cancers and while MEK inhibition can promote recruitment of tumor-infiltrating lymphocytes to the tumor, here we show that MEK inhibition adversely affects early onset T-cell effector function. We show that α-4-1BB and α-OX-40 T-cell agonist antibodies can rescue the adverse effects of MEK inhibition on T cells in both mouse and human T cells, which results in augmented anti-tumor effects in vivo...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28924054/immunosurveillance-and-immunoediting-of-breast-cancer-via-class-i-mhc-receptors
#17
Megan M Tu, Mir Munir A Rahim, Céline Sayed, Ahmad Bakur Mahmoud, Andrew P Makrigiannis
Ly49 receptors, which recognize "self" class I major histocompatibility complex (MHC-I) molecules, enable natural killer (NK) cells to detect loss of MHC-I expression on transformed and virally infected cells. The impact of NK cell-mediated MHC-I surveillance on immunoediting of breast cancer is still not fully understood. This work assesses the impact of Ly49 receptors on tumor development in terms of cancer control and in driving immune-evading cancer mutations. Genetically modified Ly49-deficient mice and those lacking NK cells through antibody depletion were less able to control E0771-derived mammary tumors in an MHC-I-dependent fashion...
September 18, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28915659/data-driven-analysis-of-immune-infiltrate-in-a-large-cohort-of-breast-cancer-and-its-association-with-disease-progression-er-activity-and-genomic-complexity
#18
Ruth Dannenfelser, Marianne Nome, Andliena Tahiri, Josie Ursini-Siegel, Hans Kristian Moen Vollan, Vilde D Haakensen, Åslaug Helland, Bjørn Naume, Carlos Caldas, Anne-Lise Børresen-Dale, Vessela N Kristensen, Olga G Troyanskaya
The tumor microenvironment is now widely recognized for its role in tumor progression, treatment response, and clinical outcome. The intratumoral immunological landscape, in particular, has been shown to exert both pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active or silent tumors may be an important indication for administration of therapy, and detecting early infiltration patterns may uncover factors that contribute to early risk. Thus far, direct detailed studies of the cell composition of tumor infiltration have been limited; with some studies giving approximate quantifications using immunohistochemistry and other small studies obtaining detailed measurements by isolating cells from excised tumors and sorting them using flow cytometry...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913760/impact-of-histopathology-tumor-infiltrating-lymphocytes-and-adjuvant-chemotherapy-on-prognosis-of-triple-negative-breast-cancer
#19
Roberto A Leon-Ferre, Mei-Yin Polley, Heshan Liu, Judith A Gilbert, Victoria Cafourek, David W Hillman, Ahmed Elkhanany, Margaret Akinhanmi, Jenna Lilyquist, Abigail Thomas, Vivian Negron, Judy C Boughey, Minetta C Liu, James N Ingle, Krishna R Kalari, Fergus J Couch, Daniel W Visscher, Matthew P Goetz
BACKGROUND: Given its high recurrence risk, guidelines recommend systemic therapy for most patients with early-stage triple-negative breast cancer (TNBC). While some clinicopathologic factors and tumor-infiltrating lymphocytes (TILs) are known to be prognostic in patients receiving chemotherapy, their prognostic implications in systemically untreated patients remain unknown. METHODS: From a cohort of 9982 women with surgically treated non-metastatic breast cancer, all patients with clinically reported ER-negative/borderline (≤10%) disease were selected for central assessment of ER/PR/HER2, histopathology, Ki-67, and TILs...
September 14, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28913723/therapeutic-implications-of-the-molecular-and-immune-landscape-of-triple-negative-breast-cancer
#20
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
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