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Mehrdad Rakaee, Lill-Tove Busund, Erna-Elise Paulsen, Elin Richardsen, Samer Al-Saad, Sigve Andersen, Tom Donnem, Roy M Bremnes, Thomas K Kilvaer
Recent data indicate that tumor-associated neutrophils (TANs) serve a dual role in tumor progression and regression. CD66b is a neutrophil marker and has been associated with patient outcome in various cancers. However, its clinical impact in non-small cell lung cancer (NSCLC) remains controversial. 536 NSCLC patients, of which 172 harbored lymph node metastases, were included in this study. Tissue microarrays were constructed and multiplexed immunohistochemistry of CD66b, CD34 and pan-keratin was performed to evaluate the localization and quantity of CD66b+ TANs...
September 30, 2016: Oncotarget
Fabienne Hermitte
No abstract text is available yet for this article.
2016: Journal for Immunotherapy of Cancer
J Galon, B A Fox, C B Bifulco, G Masucci, T Rau, G Botti, F M Marincola, G Ciliberto, F Pages, P A Ascierto, M Capone
The fifth "Melanoma Bridge Meeting" took place in Naples, December 1-5th, 2015. The main topics discussed at this meeting were: Molecular and Immuno advances, Immunotherapies and Combination Therapies, Tumor Microenvironment and Biomarkers and Immunoscore. The natural history of cancer involves interactions between the tumor and the immune system of the host. The immune infiltration at the tumor site may be indicative of host response. Significant correlations were shown between the levels of immune cell infiltration in tumors and patient's clinical outcome...
2016: Journal of Translational Medicine
Xuan Sun, Jian Suo, Jun Yan
Human colorectal cancer (CRC) is the third most commonly diagnosed malignancies and the prognosis for patients with recurrent or metastatic disease is extremely poor. Although new chemotherapeutic regimen improves survival rates, therapy with better efficacy and less adverse effects is drastically needed. Immunotherapy has been investigated in human CRC for decades with limited success. However, recent developments of immunotherapy, particularly immune checkpoint inhibitor therapy, have achieved promising clinical benefits in many types of cancer and revived the hope for utilizing such therapy in human CRC...
July 28, 2016: World Journal of Gastroenterology: WJG
Ibraheem O Awowole, Olufemiwa N Makinde, Olusegun O Badejoko, Ganiyat O Omoniyi-Esan, Aramide M Tijani, Kayode O Ajenifuja, Olabisi M Loto
OBJECTIVE: To compare the expression of estrogen receptor α (ERα) and progesterone receptor (PR) in myometrium and leiomyomata tissue, and to correlate their expression with symptoms of uterine leiomyomata. METHODS: In a cross-sectional study, intraoperative biopsy samples of leiomyomata and adjacent myometrial specimens were obtained from premenopausal women with uterine leiomyomata treated at a center in Nigeria between September 2013 and August 2014. Immunohistochemistry for ERα and PR expression was performed on the samples...
August 24, 2016: International Journal of Gynaecology and Obstetrics
Cristina Migali, Monica Milano, Dario Trapani, Carmen Criscitiello, Angela Esposito, Marzia Locatelli, Ida Minchella, Giuseppe Curigliano
Is breast cancer (BC) immunogenic? Many data suggest that it is. Many observations demonstrated the prognostic role of tumor-infiltrating lymphocytes (TILs) in triple negative (TN) and human epidermal growth factor receptor 2 (HER-2)-positive BC. TNBCs are poorly differentiated tumors with high genetic instability and very high heterogeneity. This heterogeneity enhances the 'danger signals' and select clone variants that could be more antigenic or, in other words, that could more strongly stimulate a host immune antitumor response...
September 2016: Therapeutic Advances in Medical Oncology
Benedetto Farsaci, Renee N Donahue, Italia Grenga, Lauren M Lepone, Peter S Kim, Brendan Dempsey, Janet C Siebert, Nuhad K Ibrahim, Ravi A Madan, Christopher R Heery, James L Gulley, Jeffrey Schlom
Tumor immunoscore analyses, especially for primary colorectal cancer and melanoma lesions, provide valuable prognostic information. Metastatic lesions of many carcinoma types, however, are often not easily accessible. We hypothesized that immune cells in peripheral blood may differ among individual patients with metastatic disease, which, in turn, may influence their response to immunotherapy. We thus analyzed immune cell subsets within peripheral blood mononuclear cells to determine if a "peripheral immunoscore" could have any prognostic significance for patients before receiving immunotherapy...
September 2, 2016: Cancer Immunology Research
Emilie Dalloneau, Nadine Baroukh, Konstantinos Mavridis, Agnès Maillet, Fabien Gueugnon, Yves Courty, Agnès Petit, Thomas Kryza, Maguy Del Rio, Serge Guyetant, Diana Carolina Cadena Castaneda, Christine Dhommée, Christophe Arnoult, Andreas Scorilas, Valérie Gouilleux-Gruart, Nathalie Heuzé-Vourc'h
Lung cancer is the leading cause of cancer-related death worldwide. Although the recommended tumor, node and metastasis (TNM) classification and stage determination are important to select therapeutic options for patients with non-small cell lung carcinoma (NSCLC), additional molecular markers are required to indicate the prognosis, in particular within a specific stage, and help with the management of patients.Because neonatal Fc receptor (FcRn) has recently been involved in colon cancer immunosurveillance, we measured its expression in non-cancerous and NSCLC lung tissues and evaluated its prognostic value in overall survival for patient with NSCLC...
June 15, 2016: Oncotarget
D Buka, J Dvořák, V Sitorová, J Hátlová, I Richter, I Sirák
BACKGROUND: The goal of this study is to examine the effect of neoadjuvant radiochemotherapy on the density of CD8(+) tumor infiltrating lymphocytes (TILs) in endoscopical biopsies and resection specimens from patients with rectal adenocarcinoma before and after therapy. PATIENTS AND METHODS: In total, 53 patients with locally advanced rectal cancer were studied. RESULTS: The median density of CD8(+) TILs in pretreatment biopsies was 12 (1- 232) and that in surgical specimens after radiochemotherapy was 18 (1- 319)...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
J H Park, D C McMillan, J Edwards, P G Horgan, C S D Roxburgh
The aim of the present study was to compare the clinical utility of two measures of the inflammatory cell infiltrate - a H&E-based assessment of the generalized inflammatory cell infiltrate (the Klintrup-Mäkinen (KM) grade), and an immunohistochemistry-based assessment of combined CD3(+) and CD8(+) T-cell density (the "Immunoscore"), in conjunction with assessment of the tumor stroma percentage (TSP) in patients undergoing resection of stage I-III colorectal cancer (CRC). Two hundred and forty-six patients were identified from a prospectively maintained database of CRC resections in a single surgical unit...
March 2016: Oncoimmunology
Sümeyye Ekmekci, Nur Olgun, Erdener Özer
OBJECTIVE: Prognostic parameters in determining risk groups for treatment in neuroblastoma are cellular differentiation, mitosis karyorrhexis index (MKI), N-myc amplification and age. However, additional prognosticators are still needed because patients can show unpredictable biological behavior. We aimed to study the prognostic significance of apoptotic activity in neuroblastomas. MATERIAL AND METHOD: Thirty-five primary neuroblastoma were evaluated. The data including stage, treatment protocol, metastatic disease, survival, N-myc status, age and prognostic categorization were obtained from the clinical records...
2016: Türk Patoloji Dergisi
Amos Kirilovsky, Florence Marliot, Carine El Sissy, Nacilla Haicheur, Jérôme Galon, Franck Pagès
The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumor, nodes, metastasis (TNM) classification system based on tumor features is used for prognosis estimation and treatment recommendations in most cancers. However, the clinical outcome can vary significantly among patients within the same tumor stage and TNM classification does not predict response to therapy. Therefore, many efforts have been focused on the identification of new markers. Multiple tumor cell-based approaches have been proposed but very few have been translated into the clinic...
August 2016: International Immunology
Celso Santos, Maria Dos Anjos Pires, Dario Santos, Rita Payan-Carreira
Superoxide dismutase (SOD) and glutathione peroxidase (GPx) are two important antioxidant enzymes involved in tissue homeostasis by protecting cells and tissues from an accumulation of reactive oxygen species. Information concerning antioxidant enzymes in the canine uterus is almost inexistent. This work intends to establish the pattern of distribution of SOD1 and GPx1 immunoreaction in canine endometrium throughout the estrous cycle, using 46 endometrium samples of healthy dogs representing different cycle stages (anestrus-10, proestrus-10, estrus-10, early diestrus-7, and diestrus-9)...
August 2016: Theriogenology
Julia Dorn, Alexandra Yassouridis, Axel Walch, Eleftherios P Diamandis, Manfred Schmitt, Marion Kiechle, Ping Wang, Enken Drecoll, Barbara Schmalfeldt, Daniela Loessner, Matthias Kotzsch, Viktor Magdolen
Members of the human kallikrein-related peptidase (KLK) family, including KLK5, have been reported to play an important role in ovarian cancer progression. In the present study, we assessed KLK5 protein expression in ovarian cancer tissues by immunohistochemistry (IHC) and ELISA, and analyzed its association with clinicopathologic parameters and disease outcome in 95 patients with advanced ovarian cancer FIGO stage III/IV. KLK5 immunoexpression was evaluated in ovarian cancer tissue microarrays by IHC using a manual semiquantitative scoring system...
2016: American Journal of Cancer Research
Bernhard Mlecnik, Gabriela Bindea, Helen K Angell, Pauline Maby, Mihaela Angelova, David Tougeron, Sarah E Church, Lucie Lafontaine, Maria Fischer, Tessa Fredriksen, Maristella Sasso, Amélie M Bilocq, Amos Kirilovsky, Anna C Obenauf, Mohamad Hamieh, Anne Berger, Patrick Bruneval, Jean-Jacques Tuech, Jean-Christophe Sabourin, Florence Le Pessot, Jacques Mauillon, Arash Rafii, Pierre Laurent-Puig, Michael R Speicher, Zlatko Trajanoski, Pierre Michel, Richard Sesboüe, Thierry Frebourg, Franck Pagès, Viia Valge-Archer, Jean-Baptiste Latouche, Jérôme Galon
Microsatellite instability in colorectal cancer predicts favorable outcomes. However, the mechanistic relationship between microsatellite instability, tumor-infiltrating immune cells, Immunoscore, and their impact on patient survival remains to be elucidated. We found significant differences in mutational patterns, chromosomal instability, and gene expression that correlated with patient microsatellite instability status. A prominent immune gene expression was observed in microsatellite-instable (MSI) tumors, as well as in a subgroup of microsatellite-stable (MSS) tumors...
March 15, 2016: Immunity
Andrew Gabrielson, Yunan Wu, Hongkun Wang, Jiji Jiang, Bhaskar Kallakury, Zoran Gatalica, Sandeep Reddy, David Kleiner, Thomas Fishbein, Lynt Johnson, Eddie Island, Rohit Satoskar, Filip Banovac, Reena Jha, Jaydeep Kachhela, Perry Feng, Tiger Zhang, Anteneh Tesfaye, Petra Prins, Christopher Loffredo, John Marshall, Louis Weiner, Michael Atkins, Aiwu Ruth He
Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3(+)) and cytotoxic (CD8(+)) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS)...
May 2016: Cancer Immunology Research
Thomas R Gill, Mohammad D Samy, Shanitra N Butler, James A Mauro, Wade J Sexton, George Blanck
Tumor immunoscoring is rapidly becoming a universal parameter of prognosis, and T-cells isolated from tumor masses are used for ex vivo amplification and readministration to patients to facilitate an antitumor immune response. We recently exploited the cancer genome atlas (TCGA) RNASeq data to assess T-cell receptor (TcR) expression and, in particular, discovered strong correlations between major histocompatibility class II (MHCII) and TcR-α constant region expression levels. In this article, we describe the results of searching TCGA exome files for TcR-α V-regions, followed by searching the V-region datasets for TcR-α-J regions...
2016: Cancer Informatics
Anna S Berghoff, Elisabeth Fuchs, Gerda Ricken, Bernhard Mlecnik, Gabriela Bindea, Thomas Spanberger, Monika Hackl, Georg Widhalm, Karin Dieckmann, Daniela Prayer, Amelie Bilocq, Harald Heinzl, Christoph Zielinski, Rupert Bartsch, Peter Birner, Jerome Galon, Matthias Preusser
The immune microenvironment of the brain differs from that of other organs and the role of tumor-infiltrating lymphocytes (TILs) in brain metastases (BM), one of the most common and devastating complication of cancer, is unclear. We investigated TIL subsets and their prognostic impact in 116 BM specimens using immunohistochemistry for CD3, CD8, CD45RO, FOXP3, PD1 and PD-L1. The Immunoscore was calculated as published previously. Overall, we found TIL infiltration in 115/116 (99.1%) BM specimens. PD-L1 expression was evident in 19/67 (28...
2016: Oncoimmunology
Etienne Becht, Nicolas A Giraldo, Claire Germain, Aurélien de Reyniès, Pierre Laurent-Puig, Jessica Zucman-Rossi, Marie-Caroline Dieu-Nosjean, Catherine Sautès-Fridman, Wolf H Fridman
The outcome of tumors results from genetic and epigenetic modifications of the transformed cells and also from the interactions of the malignant cells with their tumor microenvironment (TME), which includes immune and inflammatory cells. For a given cancer type, the composition of the immunological TME is not homogeneous. Heterogeneity is found between different cancer types and also between tumors from patients with the same type of cancer. Some tumors exhibit a poor infiltration by immune cells, and others are highly infiltrated by lymphocytes...
2016: Advances in Immunology
Bernhard Mlecnik, Gabriela Bindea, Amos Kirilovsky, Helen K Angell, Anna C Obenauf, Marie Tosolini, Sarah E Church, Pauline Maby, Angela Vasaturo, Mihaela Angelova, Tessa Fredriksen, Stéphanie Mauger, Maximilian Waldner, Anne Berger, Michael R Speicher, Franck Pagès, Viia Valge-Archer, Jérôme Galon
Although distant metastases account for most of the deaths in cancer patients, fundamental questions regarding mechanisms that promote or inhibit metastasis remain unanswered. We show the impact of mutations, genomic instability, lymphatic and blood vascularization, and the immune contexture of the tumor microenvironment on synchronous metastases in large cohorts of colorectal cancer patients. We observed large genetic heterogeneity among primary tumors, but no major differences in chromosomal instability or key cancer-associated mutations...
February 24, 2016: Science Translational Medicine
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