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J Benzaquen, C-H Marquette, N Glaichenhaus, S Leroy, P Hofman, M Ilié
INTRODUCTION: Immunotherapy aims to promote the immune system's activity against malignant cells by stimulating the response to several tumor antigens. STATE OF THE ART: Immunosurveillance may adjust the immunogenicity of tumors. To be effective, immunity must induce the specific activation of CD4+ and CD8+ T lymphocytes, as well as activation of innate immunity. Activator and inhibitory costimulatory molecules regulate T lymphocyte activation at immunity checkpoints such as PD-1/PD-L1 and CTLA-4...
February 7, 2018: Revue des Maladies Respiratoires
Florian Posch, Karina Silina, Sebastian Leibl, Axel Mündlein, Holger Moch, Alexander Siebenhüner, Panagiotis Samaras, Jakob Riedl, Michael Stotz, Joanna Szkandera, Herbert Stöger, Martin Pichler, Roger Stupp, Maries van den Broek, Peter Schraml, Armin Gerger, Ulf Petrausch, Thomas Winder
Tertiary lymphoid structures (TLS) are associated with favorable outcome in non-metastatic colorectal carcinoma (nmCRC), but the dynamics of TLS maturation and its association with effective anti-tumor immune surveillance in nmCRC are unclear. Here, we hypothesized that not only the number of TLS but also their composition harbors information on recurrence risk in nmCRC. In a comprehensive molecular, tissue, laboratory, and clinical analysis of 109 patients with stage II/III nmCRC, we assessed TLS numbers and degree of maturation in surgical specimens by multi-parameter immunofluorescence of follicular dendritic cell (FDC) and germinal center (GC) markers...
2018: Oncoimmunology
Sigurd M Hald, Mehrdad Rakaee, Inigo Martinez, Elin Richardsen, Samer Al-Saad, Erna-Elise Paulsen, Egil Støre Blix, Thomas Kilvaer, Sigve Andersen, Lill-Tove Busund, Roy M Bremnes, Tom Donnem
BACKGROUND: Lymphocyte activation gene-3 (LAG-3) is an immune checkpoint receptor and a putative therapeutic target in non-small-cell lung cancer (NSCLC). We explored the prognostic effect of LAG-3+ tumor-infiltrating lymphocytes (TILs) in primary tumors and metastatic lymph nodes in NSCLC and its potential for inclusion in an immunoscore, supplementing the TNM classification. MATERIALS AND METHODS: Primary tumor tissue from 553 stage I-IIIB NSCLC patients and 143 corresponding metastatic lymph nodes were collected...
December 11, 2017: Clinical Lung Cancer
Kyösti Tahkola, Jukka-Pekka Mecklin, Erkki-Ville Wirta, Maarit Ahtiainen, Olli Helminen, Jan Böhm, Ilmo Kellokumpu
Increasing evidence suggests that cancer progression is strongly influenced by host immune response, which is represented by immune cell infiltrates. T-lymphocyte-based immunoscore has proved to be a prognostic factor in colon cancer, but its significance in pancreatic cancer is poorly known. Total of 108 patients operated (R0/R1) for pancreatic ductal adenocarcinoma (PDAC) (TNM stage I-II) were included in the study. Immune cell score (IS) was determined by scoring the samples from grade 0 to 4 according to the number of immune cells (CD3+ and CD8+) in tumor core and invasion margin using tissue microarrays, immunohistochemistry, and digital analysis...
January 22, 2018: Virchows Archiv: An International Journal of Pathology
K M Marks, N P West, E Morris, P Quirke
BACKGROUND: Numerous factors affect the prognosis of colorectal cancer (CRC), many of which have long been identified, such as patient demographics and the multidisciplinary team. In more recent years, molecular and immunological biomarkers have been shown to have a significant influence on patient outcomes. Whilst some of these biomarkers still require ongoing validation, if proven to be worthwhile they may change our understanding and future management of CRC. The aim of this review was to identify the key prognosticators of CRC, including new molecular and immunological biomarkers, and outline how these might fit into the whole wider context for patients...
January 2018: British Journal of Surgery
Sarah E Church, Jérôme Galon
The tumor microenvironment consists of a complex milieu of cells and factors that maintain equilibrium between tumor progression and destruction. Characterization of the immune contexture in primary tumors has consistently shown that T lymphocytes are an integral predictor of improved clinical outcome. This is notably true in colorectal carcinoma where high densities of cytotoxic or memory T lymphocytes in the invasive margin and the center of the primary tumor predict better patient survival, a measure termed Immunoscore...
2017: Advances in Experimental Medicine and Biology
Yun Wang, Hao-Cheng Lin, Ma-Yan Huang, Qiong Shao, Zhi-Qiang Wang, Feng-Hua Wang, Yun-Fei Yuan, Bin-Kui Li, De-Shen Wang, Pei-Rong Ding, Gong Chen, Xiao-Jun Wu, Zhen-Hai Lu, Li-Ren Li, Zhi-Zhong Pan, Peng Sun, Shu-Mei Yan, De-Sen Wan, Rui-Hua Xu, Yu-Hong Li
BACKGROUND: The Immunoscore was initially established to evaluate the prognosis of stage I/II/III colorectal cancer patients. However, the feasibility of the Immunoscore for the prognosis of colorectal cancer liver metastases (CRCLM) has not been reported. METHODS: Liver metastases in 249 CRCLM patients were retrospectively analyzed. The Immunoscore was assessed according to the counts and densities of CD3+ and CD8+ T cells in the central- and peritumoral areas by immunohistochemistry...
March 2018: Cancer Immunology, Immunotherapy: CII
Janis M Taube, Jérôme Galon, Lynette M Sholl, Scott J Rodig, Tricia R Cottrell, Nicolas A Giraldo, Alexander S Baras, Sanjay S Patel, Robert A Anders, David L Rimm, Ashley Cimino-Mathews
Characterizing the tumor immune microenvironment enables the identification of new prognostic and predictive biomarkers, the development of novel therapeutic targets and strategies, and the possibility to guide first-line treatment algorithms. Although the driving elements within the tumor microenvironment of individual primary organ sites differ, many of the salient features remain the same. The presence of a robust antitumor milieu characterized by an abundance of CD8+ cytotoxic T-cells, Th1 helper cells, and associated cytokines often indicates a degree of tumor containment by the immune system and can even lead to tumor elimination...
February 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Yu Zhou, Juan Du, Hong-Yan Hou, Yan-Fang Lu, Jing Yu, Li-Yan Mao, Feng Wang, Zi-Yong Sun
Tuberculosis (TB) is a leading global public health problem. To achieve the end TB strategy, non-invasive markers for diagnosis and treatment monitoring of TB disease are urgently needed, especially in high-endemic countries such as China. Interferon-gamma release assays (IGRAs) and tuberculin skin test (TST), frequently used immunological methods for TB detection, are intrinsically unable to discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). Thus, the specificity of these methods in the diagnosis of ATB is dependent upon the local prevalence of LTBI...
2017: Frontiers in Cellular and Infection Microbiology
Jerome Galon, Alessandro Lugli, Carlo Bifulco, Franck Pages, Giuseppe Masucci, Francesco M Marincola, Paolo A Ascierto
The predictive accuracy of the traditional staging system is based on disease progression as a tumour cell-autonomous process, but it fails to incorporate the effects of the host immune response. A precise analysis of the immune component of the tumour microenvironment by computer-based analysis may be essential to managing patients better, opening the road to an expertise in this new emerging field. The Immunoscore as a new possible approach in the classification of cancer, designated TNM-Immune, studied in colon cancer patients with predictive and prognostic value...
October 20, 2017: Journal of Translational Medicine
Khinh Ranh Voong, Josephine Feliciano, Daniel Becker, Benjamin Levy
Recently, a firmer understanding of tumor immunology and tumor escape mechanisms has led to the development of immune checkpoint inhibitors, antibodies against programmed death-1 (PD-1) and its ligand (PD-L1). Nivolumab, pembrolizumab, and atezolizumab have dramatically altered the treatment paradigm in non-small cell lung cancer (NSCLC) and have each demonstrated improvements in outcomes and quality of life when compared to chemotherapy. Enrichment strategies to better select those patients more likely to respond have identified PD-L1 staining by immunohistochemistry (IHC) to be a predictive biomarker in both treatment naïve and refractory patients...
September 2017: Annals of Translational Medicine
Dung T Le, Vanessa M Hubbard-Lucey, Michael A Morse, Christopher R Heery, Andrea Dwyer, Thomas H Marsilje, Arthur N Brodsky, Emily Chan, Dustin A Deming, Luis A Diaz, Wolf H Fridman, Richard M Goldberg, Stanley R Hamilton, Franck Housseau, Elizabeth M Jaffee, S Peter Kang, Smitha S Krishnamurthi, Christopher H Lieu, Wells Messersmith, Cynthia L Sears, Neil H Segal, Arvin Yang, Rebecca A Moss, Edward Cha, Jill O'Donnell-Tormey, Nancy Roach, Anjelica Q Davis, Keavy McAbee, Sharyn Worrall, Al B Benson
Immunotherapy is rapidly becoming a standard of care for many cancers. However, colorectal cancer had been generally resistant to immunotherapy, despite features in common with sensitive tumors. Observations of substantial clinical activity for checkpoint blockade in colorectal cancers with defective mismatch repair (microsatellite instability-high tumors) have reignited interest in the search for immunotherapies that could be extended to the larger microsatellite stable (MSS) population. The Cancer Research Institute and Fight Colorectal Cancer convened a group of scientists, clinicians, advocates, and industry experts in colorectal cancer and immunotherapy to compile ongoing research efforts, identify gaps in translational and clinical research, and provide a blueprint to advance immunotherapy...
October 16, 2017: Cancer Immunology Research
Hidenobu Ishii, Koichi Azuma, Akihiko Kawahara, Norikazu Matsuo, Takaaki Tokito, Takashi Kinoshita, Kazuhiko Yamada, Tetsuro Sasada, Jun Akiba, Tomoaki Hoshino
Programmed cell death 1 (PD-1) receptor-ligand interaction is a major pathway that is often hijacked by tumors to suppress immune control. Immunoscore (IS), a combinational index of CD3 and CD8 tumor-infiltrating lymphocyte (TIL) density in the tumor's center and invasive margin, is a new prognostic tool suggested to be superior to conventional tumor-staging methods in various tumors. This retrospective study aimed to investigate the prevalence and prognostic roles of PD-ligand 1 (PD-L1) expression and IS in non-small cell lung cancer (NSCLC) patients receiving adjuvant chemotherapy...
September 22, 2017: Oncotarget
Kyung-Ju Kim, Han Kwang Yang, Woo Ho Kim, Gyeong Hoon Kang
BACKGROUND: The aim of this study was to evaluate how programmed death-ligand-1 (PD-L1) expression is linked to the immunoscore in the context of the tumor microenvironment and to assess the differential prognostic value of PD-L1 expression according to the immunoscore in 153 patients with microsatellite instability-high (MSI-H) advanced gastric cancer (GC). RESULTS: We found that T-PD-L1 (+) and I-PD-L1 (+) were significantly associated with a high immunoscore...
August 29, 2017: Oncotarget
Deepa Rajesh Mane, Alka D Kale, Chetan Belaldavar
BACKGROUND: Immunohistochemistry (IHC) is a molecular technique that has grown tremendously over the years. However, the assessment is only qualitative which is subjective and causes errors. Due to this limitation, several excellent markers have not gained importance and reached clinical trials. Hence, we aimed to quantify IHC by ImageJ analysis with a novel IHC profiler plugin. ImageJ has not been tried in oral precancerous tissues with minimal attempt for matrix markers. AIM: This study aimed to validate the quantification of immunoexpression of tenascin-C (TN-C) in oral precancerous tissues and oral squamous cell carcinoma (OSCC) using ImageJ software with IHC profiler plugin...
May 2017: Journal of Oral and Maxillofacial Pathology: JOMFP
Laetitia Marisa, Magali Svrcek, Ada Collura, Etienne Becht, Pascale Cervera, Kristell Wanherdrick, Olivier Buhard, Anastasia Goloudina, Vincent Jonchère, Janick Selves, Gerard Milano, Dominique Guenot, Romain Cohen, Chrystelle Colas, Pierre Laurent-Puig, Sylviane Olschwang, Jérémie H Lefèvre, Yann Parc, Valérie Boige, Côme Lepage, Thierry André, Jean-François Fléjou, Valentin Dérangère, François Ghiringhelli, Aurélien de Reynies, Alex Duval
Background: Immune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore. Methods: The expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI)...
January 1, 2018: Journal of the National Cancer Institute
Bernhard Mlecnik, Marc Van den Eynde, Gabriela Bindea, Sarah E Church, Angela Vasaturo, Tessa Fredriksen, Lucie Lafontaine, Nacilla Haicheur, Florence Marliot, Daphné Debetancourt, Géraldine Pairet, Anne Jouret-Mourin, Jean-Francois Gigot, Catherine Hubert, Etienne Danse, Cristina Dragean, Javier Carrasco, Yves Humblet, Viia Valge-Archer, Anne Berger, Franck Pagès, Jean-Pascal Machiels, Jérôme Galon
Background: This study assesses how the metastatic immune landscape is impacting the response to treatment and the outcome of colorectal cancer (CRC) patients. Methods: Complete curative resection of metastases (n = 441) was performed for two patient cohorts (n = 153). Immune densities were quantified in the center and invasive margin of all metastases. Immunoscore and T and B cell (TB) score were analyzed in relation to radiological and pathological responses and patient's disease-free (DFS) and overall survival (OS) using multivariable Cox proportional hazards models...
January 1, 2018: Journal of the National Cancer Institute
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
Cédric Panje, Oliver Riesterer, Christoph Glanzmann, Gabriela Studer
BACKGROUND: Volumetric tumor staging has been shown as superior prognostic tool compared to the conventional TNM system in patients undergoing definitive intensity-modulated radiotherapy (IMRT) for head and neck cancer. Recently, clinical immunoscores such as the neutrophil-lymphocyte ratio (NLR) have been investigated as prognostic markers in several tumor entities. The aim of this study was to assess the combined prognostic value of NLR and tumor volume in patients treated with IMRT for oropharyngeal cancer (OC)...
September 11, 2017: BMC Cancer
Erkki-Ville Wirta, Toni Seppälä, Marjukka Friman, Juha Väyrynen, Maarit Ahtiainen, Hannu Kautiainen, Teijo Kuopio, Ilmo Kellokumpu, Jukka-Pekka Mecklin, Jan Böhm
The aim of this study was to investigate immune response and its prognostic significance in colon carcinomas using the previously described Immunoscore (IS). A population-based series of 779 colorectal cancers, operated on between 2000 and 2010, were classified according to tumour, node, metastasis (TNM) status, mismatch repair (MMR), and BRAF mutation status. Rectal cancer cases (n = 203) were excluded as a high proportion of these patients received preoperative neoadjuvant chemoradiotherapy. Tissue microarray (TMA) samples collected from the tumour centre and invasive front were immunostained for CD3 and CD8...
July 2017: Journal of Pathology. Clinical Research
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