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https://www.readbyqxmd.com/read/28818640/the-influence-of-physical-activity-in-the-anti-tumor-immune-response-in-experimental-breast-tumor
#1
Thiago M Bianco, Douglas R Abdalla, Chamberttan S Desidério, Sofie Thys, Cindy Simoens, John-Paul Bogers, Eddie F C Murta, Márcia A Michelin
This study aimed to investigate the influence of physical activity in innate immunity to conduce to an effective antitumoral immune response analyzing the phenotype and activation status of infiltrating cells. We analyzed the intracellular cytokines and the transcription factors of tumor infiltrating lymphocytes (TILS) and spleen leukocytes. The Nos2 gene expression was evaluated in spleen cells and futhermore the ROS production was measured and spleen cells; another cell evaluated was dendritic cells (TIDCs), their cytokines expression and membrane molecules; finally to understood the results obtained, we analysed the dendritic cells obtained from bone marrow...
August 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28817603/expression-of-the-mhc-class-ii-in-triple-negative-breast-cancer-is-associated-with-tumor-infiltrating-lymphocytes-and-interferon-signaling
#2
In Ah Park, Seong-Hye Hwang, In Hye Song, Sun-Hee Heo, Young-Ae Kim, Won Seon Bang, Hye Seon Park, Miseon Lee, Gyungyub Gong, Hee Jin Lee
Tumor-infiltrating lymphocytes (TILs) have been known for their strong prognostic and predictive significance in triple-negative breast cancer (TNBC). Several mechanisms for TIL influx in TNBC have been elucidated. Major histocompatibility complex class II (MHC-II) is an essential component of the adaptive immune system and is generally restricted to the surface of antigen-presenting cells. However, it has been reported that interferon-gamma signaling may induce MHC-II in almost all cell types, including those derived from cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28799073/immunotherapy-in-breast-cancer-the-emerging-role-of-pd-1-and-pd-l1
#3
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/28794686/tumor-infiltrating-leukocyte-density-is-independent-of-tumor-grade-and-molecular-subtype-in-aggressive-breast-cancer-of-western-kenya
#4
Rispah T Sawe, Simeon K Mining, Ayub V Ofulla, Kirtika Patel, Bernard Guyah, David Chumba, Jenifer R Prosperi, Maggie Kerper, Zonggao Shi, Mayra Sandoval-Cooper, Katherine Taylor, Sunil Badve, M Sharon Stack, Laurie E Littlepage
BACKGROUND: Tumors commonly are infiltrated by leukocytes, or tumor infiltrating leukocytes (TILs). It remains unclear, however, if the density and type of individual TILs has a direct or simply correlative role in promoting poor prognosis in breast cancer patients. Breast cancer in Kenyan women is aggressive with presentation at a young age, with advanced grade (grade III), large tumor size (>2.0 cm), and poor prognosis. We previously observed that the tumors were predominantly estrogen receptor positive (ER+) but also included both a high percentage of triple negative tumors and also increased immune cell infiltration within the tumors...
2017: Tropical Medicine and Health
https://www.readbyqxmd.com/read/28777143/assessing-tumor-infiltrating-lymphocytes-in-solid-tumors-a-practical-review-for-pathologists-and-proposal-for-a-standardized-method-from-the-international-immuno-oncology-biomarkers-working-group-part-2-tils-in-melanoma-gastrointestinal-tract-carcinomas-non
#5
Shona Hendry, Roberto Salgado, Thomas Gevaert, Prudence A Russell, Tom John, Bibhusal Thapa, Michael Christie, Koen van de Vijver, M V Estrada, Paula I Gonzalez-Ericsson, Melinda Sanders, Benjamin Solomon, Cinzia Solinas, Gert G G M Van den Eynden, Yves Allory, Matthias Preusser, Johannes Hainfellner, Giancarlo Pruneri, Andrea Vingiani, Sandra Demaria, Fraser Symmans, Paolo Nuciforo, Laura Comerma, E A Thompson, Sunil Lakhani, Seong-Rim Kim, Stuart Schnitt, Cecile Colpaert, Christos Sotiriou, Stefan J Scherer, Michail Ignatiadis, Sunil Badve, Robert H Pierce, Giuseppe Viale, Nicolas Sirtaine, Frederique Penault-Llorca, Tomohagu Sugie, Susan Fineberg, Soonmyung Paik, Ashok Srinivasan, Andrea Richardson, Yihong Wang, Ewa Chmielik, Jane Brock, Douglas B Johnson, Justin Balko, Stephan Wienert, Veerle Bossuyt, Stefan Michiels, Nils Ternes, Nicole Burchardi, Stephen J Luen, Peter Savas, Frederick Klauschen, Peter H Watson, Brad H Nelson, Carmen Criscitiello, Sandra O'Toole, Denis Larsimont, Roland de Wind, Giuseppe Curigliano, Fabrice André, Magali Lacroix-Triki, Mark van de Vijver, Federico Rojo, Giuseppe Floris, Shahinaz Bedri, Joseph Sparano, David Rimm, Torsten Nielsen, Zuzana Kos, Stephen Hewitt, Baljit Singh, Gelareh Farshid, Sibylle Loibl, Kimberly H Allison, Nadine Tung, Sylvia Adams, Karen Willard-Gallo, Hugo M Horlings, Leena Gandhi, Andre Moreira, Fred Hirsch, Maria V Dieci, Maria Urbanowicz, Iva Brcic, Konstanty Korski, Fabien Gaire, Hartmut Koeppen, Amy Lo, Jennifer Giltnane, Marlon C Rebelatto, Keith E Steele, Jiping Zha, Kenneth Emancipator, Jonathan W Juco, Carsten Denkert, Jorge Reis-Filho, Sherene Loi, Stephen B Fox
Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma...
August 2, 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28777142/assessing-tumor-infiltrating-lymphocytes-in-solid-tumors-a-practical-review-for-pathologists-and-proposal-for-a-standardized-method-from-the-international-immunooncology-biomarkers-working-group-part-1-assessing-the-host-immune-response-tils-in-invasive-breast
#6
Shona Hendry, Roberto Salgado, Thomas Gevaert, Prudence A Russell, Tom John, Bibhusal Thapa, Michael Christie, Koen van de Vijver, M V Estrada, Paula I Gonzalez-Ericsson, Melinda Sanders, Benjamin Solomon, Cinzia Solinas, Gert G G M Van den Eynden, Yves Allory, Matthias Preusser, Johannes Hainfellner, Giancarlo Pruneri, Andrea Vingiani, Sandra Demaria, Fraser Symmans, Paolo Nuciforo, Laura Comerma, E A Thompson, Sunil Lakhani, Seong-Rim Kim, Stuart Schnitt, Cecile Colpaert, Christos Sotiriou, Stefan J Scherer, Michail Ignatiadis, Sunil Badve, Robert H Pierce, Giuseppe Viale, Nicolas Sirtaine, Frederique Penault-Llorca, Tomohagu Sugie, Susan Fineberg, Soonmyung Paik, Ashok Srinivasan, Andrea Richardson, Yihong Wang, Ewa Chmielik, Jane Brock, Douglas B Johnson, Justin Balko, Stephan Wienert, Veerle Bossuyt, Stefan Michiels, Nils Ternes, Nicole Burchardi, Stephen J Luen, Peter Savas, Frederick Klauschen, Peter H Watson, Brad H Nelson, Carmen Criscitiello, Sandra O'Toole, Denis Larsimont, Roland de Wind, Giuseppe Curigliano, Fabrice André, Magali Lacroix-Triki, Mark van de Vijver, Federico Rojo, Giuseppe Floris, Shahinaz Bedri, Joseph Sparano, David Rimm, Torsten Nielsen, Zuzana Kos, Stephen Hewitt, Baljit Singh, Gelareh Farshid, Sibylle Loibl, Kimberly H Allison, Nadine Tung, Sylvia Adams, Karen Willard-Gallo, Hugo M Horlings, Leena Gandhi, Andre Moreira, Fred Hirsch, Maria V Dieci, Maria Urbanowicz, Iva Brcic, Konstanty Korski, Fabien Gaire, Hartmut Koeppen, Amy Lo, Jennifer Giltnane, Marlon C Rebelatto, Keith E Steele, Jiping Zha, Kenneth Emancipator, Jonathan W Juco, Carsten Denkert, Jorge Reis-Filho, Sherene Loi, Stephen B Fox
Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear. In part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment...
September 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28750133/role-of-cytotoxic-tumor-infiltrating-lymphocytes-in-predicting-outcomes-in-metastatic-her2-positive-breast-cancer-a-secondary-analysis-of-a-randomized-clinical-trial
#7
Shuzhen Liu, Bingshu Chen, Samantha Burugu, Samuel Leung, Dongxia Gao, Shakeel Virk, Zuzana Kos, Wendy R Parulekar, Lois Shepherd, Karen A Gelmon, Torsten O Nielsen
Importance: Accumulating evidence indicates that tumor-infiltrating lymphocytes (TILs) are associated with clinical outcomes and may predict the efficacy of chemotherapy and human epidermal growth factor receptor 2 (HER2, encoded by the gene ERBB2)-targeted therapy in patients with HER2-positive breast cancer. Objective: To investigate the role of TILs, particularly cytotoxic CD8+ T cells, in the prediction of outcomes in patients with HER2-positive metastatic breast cancer randomized to an antibody-based (trastuzumab) vs a small molecule-based (lapatinib) anti-HER2 therapy...
July 27, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28735162/tumor-infiltrating-lymphocytes-in-breast-cancer-according-to-tumor-subtype-current-state-of-the-art
#8
REVIEW
Cinzia Solinas, Luisa Carbognin, Pushpamali De Silva, Carmen Criscitiello, Matteo Lambertini
The recent success of the immune checkpoint blockade in cancer immunotherapy has modified the treatment algorithms in a variety of aggressive neoplastic diseases. Nevertheless, optimal selection of ideal candidates to these drugs remains a challenge. The presence, location and composition of a pre-existing tumor immune infiltrate seem to impact on the benefit from these treatments. The association between the presence of baseline tumor-infiltrating lymphocytes (TIL) and patients' outcomes has been widely investigated in breast cancer, although immunotherapeutic strategies have historically been less successful with respect to other neoplastic diseases such as melanoma and kidney cancer...
July 20, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28731046/pd-l1-expression-and-the-immune-microenvironment-in-primary-invasive-lobular-carcinomas-of-the-breast
#9
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/28723659/data-driven-analysis-of-immune-infiltrate-in-a-large-cohort-of-breast-cancer-and-its-association-with-disease-progression-er-activity-and-genomic-complexity
#10
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...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28714863/dna-methylation-based-immune-response-signature-improves-patient-diagnosis-in-multiple-cancers
#11
Jana Jeschke, Martin Bizet, Christine Desmedt, Emilie Calonne, Sarah Dedeurwaerder, Soizic Garaud, Alexander Koch, Denis Larsimont, Roberto Salgado, Gert Van den Eynden, Karen Willard Gallo, Gianluca Bontempi, Matthieu Defrance, Christos Sotiriou, François Fuks
BACKGROUND: The tumor immune response is increasingly associated with better clinical outcomes in breast and other cancers. However, the evaluation of tumor-infiltrating lymphocytes (TILs) relies on histopathological measurements with limited accuracy and reproducibility. Here, we profiled DNA methylation markers to identify a methylation of TIL (MeTIL) signature that recapitulates TIL evaluations and their prognostic value for long-term outcomes in breast cancer (BC). METHODS: MeTIL signature scores were correlated with clinical endpoints reflecting overall or disease-free survival and a pathologic complete response to preoperative anthracycline therapy in 3 BC cohorts from the Jules Bordet Institute in Brussels and in other cancer types from The Cancer Genome Atlas...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28706143/integrated-analysis-of-somatic-mutations-and-immune-microenvironment-of-multiple-regions-in-breast-cancers
#12
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...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28701569/distinct-tertiary-lymphoid-structure-associations-and-their-prognostic-relevance-in-her2-positive-and-negative-breast-cancers
#13
Xia Liu, Julia Y S Tsang, Thazin Hlaing, Jintao Hu, Yun-Bi Ni, Siu Ki Chan, Sai Yin Cheung, Gary M Tse
BACKGROUND: The presence of tumor infiltrating lymphocytes (TIL) is associated with favorable prognosis. Recent evidence suggested that not only their density, but also the spatial organization as tertiary lymphoid structures (TLS), play a key role in determining patient survival. MATERIALS AND METHODS: In a cohort of 248 breast cancers, the clinicopathologic association and prognostic role of TLS was examined. RESULTS: Tertiary lymphoid structures were associated with higher tumor grade, apocrine phenotype, necrosis, extensive in situ component, lymphovascular invasion (LVI), and high TIL...
July 12, 2017: Oncologist
https://www.readbyqxmd.com/read/28693173/predictive-and-prognostic-significance-of-cd8-tumor-infiltrating-lymphocytes-in-patients-with-luminal-b-her-2-negative-breast-cancer-treated-with-neoadjuvant-chemotherapy
#14
Khalid Al-Saleh, Nashwa Abd El-Aziz, Arwa Ali, Waleed Abozeed, Ahmed Abd El-Warith, Ahmed Ibraheem, Jawaher Ansari, Ammar Al-Rikabi, Sufia Husain, Jean-Marc Nabholtz
The immunobiology of breast cancer (BC) subtypes, including luminal cancer, remains unclear. Cluster of differentiation (CD)8(+) tumor-infiltrating lymphocytes (TIL) are essential components of tumor-specific cellular adaptive immunity. However, only few studies have addressed the significance of cluster of differentiation 8(+)(CD8(+)) TIL in patients with luminal BC. The present study aimed to evaluate the predictive and prognostic significance of CD8(+) TIL in patients with luminal B/human epidermal growth factor receptor 2 (HER 2)-negative BC treated with anthracycline-based neoadjuvant chemotherapy (NC)...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28675570/predicting-the-level-of-tumor-infiltrating-lymphocytes-in-patients-with-triple-negative-breast-cancer-usefulness-of-breast-mri-computer-aided-detection-and-diagnosis
#15
You Jin Ku, Hak Hee Kim, Joo Hee Cha, Hee Jung Shin, Eun Young Chae, Woo Jung Choi, Hee Jin Lee, Gyungyub Gong
PURPOSE: To evaluate the usefulness of magnetic resonance imaging (MRI) computer-aided detection and diagnosis (CAD) for the detection of tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC) patients. TNBC is a heterogeneous malignancy with a varying prognosis. Recently, the importance of TILs in TNBC has been determined. MATERIALS AND METHODS: We retrospectively enrolled 60 lesions of TNBC. Either at 1.5T or 3T MRI, including T1 , T2 -weighted, and dynamic contrast-enhanced, images were obtained...
July 4, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28674083/combining-local-immunotoxins-targeting-mesothelin-with-ctla-4-blockade-synergistically-eradicates-murine-cancer-by-promoting-anticancer-immunity
#16
Yasmin Leshem, James O'Brien, Xiufen Liu, Tapan K Bera, Masaki Terabe, Jay A Berzofsky, Birgit Bossenmaier, Gerhard Niederfellner, Chin-Hsien Tai, Yoram Reiter, Ira Pastan
Immune checkpoint blockade using antibodies to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) benefits a limited number of cancer patients. SS1P and LMB-100 are immunotoxins that target mesothelin. We observed delayed responses to SS1P in patients with mesothelioma suggesting that antitumor immunity was induced. Our goal was to stimulate antitumor immunity by combining SS1P or LMB-100 with anti-CTLA-4. We constructed a BALB/c breast cancer cell line expressing human mesothelin (66C14-M), which was implanted in one or two locations...
August 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28666979/predicting-the-response-to-ctla-4-blockade-by-longitudinal-noninvasive-monitoring-of-cd8-t-cells
#17
Mohammad Rashidian, Jessica R Ingram, Michael Dougan, Anushka Dongre, Katherine A Whang, Camille LeGall, Juan J Cragnolini, Brian Bierie, Monica Gostissa, James Gorman, Gijsbert M Grotenbreg, Atul Bhan, Robert A Weinberg, Hidde L Ploegh
Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non-small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno-positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy. We used (89)Zr-labeled PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratumoral CD8(+) T cells in the immunotherapy-susceptible B16 melanoma model in response to checkpoint blockade...
August 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28651158/prospective-validation-of-a-lymphocyte-infiltration-prognostic-test-in-stage-iii-colon-cancer-patients-treated-with-adjuvant-folfox
#18
Jean-François Emile, Catherine Julié, Karine Le Malicot, Come Lepage, Josep Tabernero, Enrico Mini, Gunnar Folprecht, Jean-Luc Van Laethem, Stéphanie Dimet, Camille Boulagnon-Rombi, Marc-Antoine Allard, Frédérique Penault-Llorca, Jaafar Bennouna, Pierre Laurent-Puig, Julien Taieb
BACKGROUND: The prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use. PATIENTS AND METHODS: According to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study...
June 23, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28649648/dramatic-response-of-metaplastic-breast-cancer-to-chemo-immunotherapy
#19
Sylvia Adams
Frequent overexpression of programmed death-ligand 1 has recently been demonstrated in metaplastic breast cancer, which is a rare breast cancer subtype with limited treatment options. This report describes the clinical course of a patient with metastatic metaplastic breast cancer who had a remarkable response to anti-programmed death-1 therapy with pembrolizumab in combination with nab-paclitaxel. Tissue correlates are presented including tumor-infiltrating lymphocytes and high-programmed death-ligand 1 expression in the tumor...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28638726/downregulation-of-antigen-presentation-associated-pathway-proteins-is-linked-to-poor-outcome-in-triple-negative-breast-cancer-patient-tumors
#20
Martin H Pedersen, Brian L Hood, Hans Christian Beck, Thomas P Conrads, Henrik J Ditzel, Rikke Leth-Larsen
Triple-negative breast cancer (TNBC) is a heterogeneous subtype with varying disease outcomes. Tumor-infiltrating lymphocytes (TILs) are frequent in TNBC and have been shown to correlate with outcome, suggesting an immunogenic component in this subtype. However, other factors intrinsic to the cancer cells may also influence outcome. To identify proteins and molecular pathways associated with recurrence in TNBC, 34 formalin-fixed paraffin-embedded (FFPE) primary TNBC tumors were investigated by global proteomic profiling using mass spectrometry...
2017: Oncoimmunology
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