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John E Mullinax, MacLean Hall, Sangeetha Prabhakaran, Jeffrey Weber, Nikhil Khushalani, Zeynep Eroglu, Andrew S Brohl, Joseph Markowitz, Erica Royster, Allison Richards, Valerie Stark, Jonathan S Zager, Linda Kelley, Cheryl Cox, Vernon K Sondak, James J Mulé, Shari Pilon-Thomas, Amod A Sarnaik
Purpose: Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience) remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL. Experimental design: Thirteen patients with metastatic melanoma were enrolled...
2018: Frontiers in Oncology
Zilong Hu, Shidong Hu, Youjun Wu, Songyan Li, Changzheng He, Xiaowei Xing, Yufeng Wang, Xiaohui Du
Although adoptive cell therapy (ACT) has demonstrated effective and remarkable clinical responses in several studies, this approach does not lead to objective clinical responses in all cases. The function of ACT is often compromised by various tumor escape mechanisms, including the accumulation of immunoregulatory cells. As a result of peritoneal metastasis in the terminal stage, malignant ascites fluid lacks effectiveness and is a poor prognostic factor for gastric cancer. The present study assessed T-cell subsets in lymphocytes derived from malignant ascites, and investigated the effects of arsenic trioxide (As2 O3 ) on regulatory T cells (Tregs) and ascites-derived tumor-infiltrating lymphocytes (TILs) in vitro ...
April 2018: Oncology Letters
Sophie Outh-Gauer, Marie Alt, Christophe Le Tourneau, Jérémy Augustin, Chloé Broudin, Cassandre Gasne, Thomas Denize, Haitham Mirghani, Elizabeth Fabre, Madeleine Ménard, Florian Scotte, Eric Tartour, Cécile Badoual
Cancer occurrence can be understood as the result of dysfunctions in immune tumoral microenvironment. Here we review the recent understandings of those microenvironment changes, regarding their causes and prognostic significance in head and neck (HN) carcinoma. We will focus on HN squamous cell cancer (SCC) and nasopharyngeal carcinomas (NPC). Their overall poor prognosis may be improved with immunotherapy in a subset of patients, as supported by current clinical trials. However, finding reliable markers of therapeutic response is crucial for patient selection, due to potential severe adverse reactions and high costs...
March 1, 2018: Cancer Treatment Reviews
Sara Bobisse, Raphael Genolet, Annalisa Roberti, Janos L Tanyi, Julien Racle, Brian J Stevenson, Christian Iseli, Alexandra Michel, Marie-Aude Le Bitoux, Philippe Guillaume, Julien Schmidt, Valentina Bianchi, Denarda Dangaj, Craig Fenwick, Laurent Derré, Ioannis Xenarios, Olivier Michielin, Pedro Romero, Dimitri S Monos, Vincent Zoete, David Gfeller, Lana E Kandalaft, George Coukos, Alexandre Harari
Immunotherapy directed against private tumor neo-antigens derived from non-synonymous somatic mutations is a promising strategy of personalized cancer immunotherapy. However, feasibility in low mutational load tumor types remains unknown. Comprehensive and deep analysis of circulating and tumor-infiltrating lymphocytes (TILs) for neo-epitope specific CD8+ T cells has allowed prompt identification of oligoclonal and polyfunctional such cells from most immunotherapy-naive patients with advanced epithelial ovarian cancer studied...
March 15, 2018: Nature Communications
Yuta Takashima, Jun Sakakibara-Konishi, Yutaka Hatanaka, Kanako C Hatanaka, Yoshihito Ohhara, Satoshi Oizumi, Yasuhiro Hida, Kichizo Kaga, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Yoshihiro Matsuno, Masaharu Nishimura
BACKGROUND: Approximately 20% to 30% of non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations are not responsive to EGFR tyrosine kinase inhibitors (TKIs). Although primary resistance to EGFR-TKIs has been attributed to various genetic alterations, little is known about the clinical and immunopathologic features of patients with primary resistance. The tumor immune microenvironment, including tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1), has been reported to play an important role in tumor progression in those with NSCLC...
February 19, 2018: Clinical Lung Cancer
Til Wykes, Eileen Joyce, Tjasa Velikonja, Andrew Watson, Gregory Aarons, Max Birchwood, Matteo Cella, Sue Dopson, David Fowler, Kathy Greenwood, Sonia Johnson, Paul McCrone, Jesus Perez, Andrew Pickles, Clare Reeder, Diana Rose, Swaran Singh, Dominic Stringer, Matthew Taylor, Rumina Taylor, Rachel Upthegrove
BACKGROUND: Cognitive problems in people with schizophrenia predict poor functional recovery even with the best possible rehabilitation opportunities and optimal medication. A psychological treatment known as cognitive remediation therapy (CRT) aims to improve cognition in neuropsychiatric disorders, with the ultimate goal of improving functional recovery. Studies suggest that intervening early in the course of the disorder will have the most benefit, so this study will be based in early intervention services, which treat individuals in the first few years following the onset of the disorder...
March 15, 2018: Trials
Leticia Wietcovsky, David Til, Rafael Alonso Salvador, Nicole Louise Lângaro Amaral, Alfred Paul Senn, Vera Lucia Lângaro Amaral
OBJECTIVE: To evaluate the efficiency of ovarian tissue heterotopic autografting after vitrification in prepubertal rats. METHODS: Fragments of excised ovaries from prepubertal rats were used after assessing post-warming cellular viability, to determine the best vitrification protocol prior to retroauricular autografting. Pre-pubertal females (N=24) were castrated and divided into three group: Group 1 - fresh ovarian tissue transplantation; Group 2 - vitrified/warmed tissue transplantation; Group 3 - bilateral oophorectomy without transplantation...
March 15, 2018: JBRA Assisted Reproduction
Xuanwei Zhang, Gabriele Niedermann
PURPOSE: Hypofractionated radiation therapy (hRT) combined with immune checkpoint blockade can induce T-cell-mediated local and abscopal antitumor effects. We had previously observed peak levels of tumor-infiltrating lymphocytes (TILs) between days 5 and 8 after hRT. Because TILs are regarded as radiosensitive, hRT schedules extending into this period might be less immunogenic, prompting us to compare clinically relevant, short and extended schedules with equivalent biologically effective doses combined with anti-programmed cell death 1 (PD1) antibody treatment...
February 3, 2018: International Journal of Radiation Oncology, Biology, Physics
Marina Alexandra Gavin Clavero, María Victoria Simón Sanz, Andrea Mur Til, Úrsula María Jariod Ferrer
PURPOSE: We conducted a review of orbital fractures treated in our hospital over a period of 4 years. We reviewed several complications of such fractures, especially the relationship of postsurgical diplopia with different presurgical variables: age, gender, type of fracture, fracture area, coronal and sagittal diameter of fracture, fractured floor area, time to surgery, presence of muscle herniation, and presence of muscle entrapment. PATIENTS AND METHODS: Fractures involving the orbital floor remain a controversial issue in terms of surgical treatment and the time from trauma to surgery...
February 19, 2018: Journal of Oral and Maxillofacial Surgery
Kimio Yonesaka, Koji Haratani, Shiki Takamura, Hitomi Sakai, Ryoji Kato, Naoki Takegawa, Takayuki Takahama, Kaoru Tanaka, Hidetoshi Hayashi, Masayuki Takeda, Shigeki Kato, Osamu Maenishi, Kazuko Sakai, Yasutaka Chiba, Takafumi Okabe, Keita Kudo, Yoshikazu Hasegawa, Hiroyasu Kaneda, Michiko Yamato, Kenji Hirotani, Masaaki Miyazawa, Kazuto Nishio, Kazuhiko Nakagawa
PURPOSE: Anti-programmed-death-1 (PD-1) immunotherapy improves survival in non-small cell lung cancer (NSCLC), but some cases are refractory to treatment, thereby requiring alternative strategies. B7-H3, an immune-checkpoint molecule, is expressed in various malignancies. To our knowledge, this study is the first to evaluate B7-H3 expression in NSCLCs treated with anti-PD-1 therapy and the therapeutic potential of a combination of anti-PD-1 therapy and B7-H3 targeting. EXPERIMENTAL DESIGN: B7-H3 expression was evaluated immunohistochemically in patients with NSCLC (n = 82), and its relationship with responsiveness to anti-PD-1 therapy and CD8+ tumor infiltrating lymphocytes (TILs) was analyzed...
March 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Jie Zhou, Zhihua Gong, Qingzhu Jia, Yan Wu, Zhen-Zhou Yang, Bo Zhu
Immunotherapy targeting the programmed cell death-1/programmed death ligand 1(PD-L1) pathway has shown promising antitumor activity in brain metastases (BMs) of non-small cell lung cancer (NSCLC) patients with an acceptable safety profile; however, the response rates often differ between primary lesions and intracranial lesions. Studies are necessary to identify detailed characterizations of the response biomarkers. In this study, we aimed to compare the differences of PD-L1 expression and CD8+ tumor-infiltrating lymphocyte (TIL) density, two major response biomarkers of PD-1/PD-L1 blockade, between paired primary and brain metastatic lesions in advanced NSCLC...
March 8, 2018: Biochemical and Biophysical Research Communications
Yanchun Li, Mateusz Opyrchal, Song Yao, Xuan Peng, Li Yan, Hossam Jabbour, Thaer Khoury
PURPOSE: The purpose of the study is to investigate the prognostic significance of programmed death ligand-1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in HER2+ breast cancer (BC). METHODS: HER2+ BC cases (n  = 191) were collected between 1996 and 2013. Tissue microarray (TMA) slides were stained with two clones of PD-L1 antibodies (28-8 and 22C3) and the percentage of positive membranous staining was scored. TILs of the full sections were also scored using percentage scale...
March 9, 2018: Breast Cancer Research and Treatment
Shinichiro Kashiwagi, Gen Tsujio, Yuka Asano, Wataru Goto, Koji Takada, Katsuyuki Takahashi, Tamami Morisaki, Hisakazu Fujita, Tsutomu Takashima, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: Recently, the concepts of progression due to pre-existing lesions (PPL) and progression due to new metastasis (PNM) have been proposed to differentiate the progression types of treatment-resistant cancers. Previously, the differences between these two progression types did not affect the determination of treatment strategies since both PPL and PNM are classified as progressive disease based on the response evaluation criteria in solid tumors (RECIST) diagnostic criteria. On the other hand, tumor infiltrating lymphocytes (TILs) are effective when used as indicators for monitoring the immune tumor microenvironment (iTME) in the cancer host, and TILs play an important role as biomarkers in predicting prognosis and therapeutic effects...
March 9, 2018: Journal of Translational Medicine
Ariadna Fabià Mayans, Josep Segarra Tomás, Helena Ascaso Til, Arnau Serra Deola, Clara Centeno Álvarez, Xavier Ruiz Plazas, Manel Prados Saavedra, José Vila Barja, Josep Maria Santillana Altimira
No abstract text is available yet for this article.
March 2018: Archivos Españoles de Urología
J Zhang, Y F Wang, B Wu, Z X Zhong, K X Wang, L Q Yang, Y Q Wang, Y Q Li, J Gao, Z S Li
BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are one of the major participants in the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC). However, the mechanism of interaction between TILs and tumors is complex and remains unclear. OBJECTIVE: To evaluate the state of immunoreactions in PDAC tissues, and explore the prognostic value of these markers in a large sample, to provide a new theoretical basis for PDAC immunotherapy. METHOD: Immunohistochemical staining of CD4+ and CD8+T cells was performed in a tissue microarray (TMA) of 143 cases of PDAC...
March 7, 2018: Current Molecular Medicine
Andrew J Sinnamon, Cimarron E Sharon, Yun Song, Madalyn G Neuwirth, David E Elder, Xiaowei Xu, Emily Y Chu, Michael E Ming, Douglas L Fraker, Phyllis A Gimotty, Giorgos C Karakousis
BACKGROUND: The immune response to melanoma is manifested locally by tumor-infiltrating lymphocytes (TILs). Men and women are known to have varying patterns of immunity, yet sex-specific prognostic implications of TILs have not been explored. METHODS: Patients with clinically localized primary melanoma ≥0.76mm in Breslow thickness who underwent sentinel lymph node (SLN) biopsy at our institution were identified. Association between TILs (absent, nonbrisk, and brisk) and SLN positivity was evaluated using logistic regression...
March 5, 2018: Journal of the American Academy of Dermatology
Jérôme Biton, Hanane Ouakrim, Agnès Dechartres, Marco Alifano, Audrey Mansuet-Lupo, Han Si, Rebecca Halpin, Todd Creasy, Claudie Bantsimba-Malanda, Jennifer Arrondeau, François Goldwasser, Pascaline Boudou-Rouquette, Ludovic Fournel, Nicolas Roche, Pierre-Régis Burgel, Jeremy Goc, Priyanka Devi-Marulkar, Claire Germain, Marie-Caroline Dieu-Nosjean, Isabelle Cremer, Ronald Herbst, Diane Damotte
RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) have a higher prevalence of lung cancer. The chronic inflammation associated with COPD probably promotes the earliest stages of carcinogenesis. However, once tumors have progressed to malignancy, the impact of COPD on the tumor immune microenvironment remains poorly defined, and its effects on immune-checkpoint blockers' efficacy are still unknown. OBJECTIVES: To study the impact of COPD on the immune contexture of non-small cell lung cancer (NSCLC)...
March 8, 2018: American Journal of Respiratory and Critical Care Medicine
Constantinos Roufas, Dimitrios Chasiotis, Anestis Makris, Christodoulos Efstathiades, Christos Dimopoulos, Apostolos Zaravinos
Background: Recently, immune-checkpoint blockade has shown striking clinical results in different cancer patients. However, a significant inter-individual and inter-tumor variability exists among different cancers. The expression of the toxins granzyme A (GZMA) and perforin 1 (PRF1), secreted by effector cytotoxic T cells and natural killer (NK) cells, were recently used as a denominator of the intratumoral immune cytolytic activity (CYT). These levels are significantly elevated upon CD8+ T-cell activation as well as during a productive clinical response against immune-checkpoint blockade therapies...
2018: Frontiers in Oncology
Robin Holtedahl
BAKGRUNN: Knesmerter er blant de vanligste årsaker til konsultasjoner for muskel- og skjelettplager. Siktemålet med denne artikkelen er dels å gi en oversikt over de siste par tiårs forskning på atraumatiske og degenerativt betingede kneplager, dels å vurdere hvorvidt den sedvanlige praksis for utredning og behandling er i samsvar med denne forskningen. KUNNSKAPSGRUNNLAG: Artikkelen er basert på et utvalg av engelskspråklige studier av atraumatiske og degenerative knelidelser funnet ved søk i Medline, manuelle søk i artiklenes litteraturlister og litteraturforslag fra Mendeley...
March 6, 2018: Tidsskrift for Den Norske Lægeforening: Tidsskrift for Praktisk Medicin, Ny Række
Til Bahadur Thapa Magar, Seung Hee Seo, Tara Man Kadayat, Hyunji Jo, Aarajana Shrestha, Ganesh Bist, Pramila Katila, Youngjoo Kwon, Eung-Seok Lee
As part of our effort to develop potential topoisomerase IIα (topo IIα) targeting anticancer agents, we systematically designed a new series of hydroxy and chloro-substituted 2,4-diphenyl 5H-chromeno[4,3-b]pyridines. Total eighteen compounds were synthesized and tested for their ability to inhibit the function of topo I and IIα, and proliferation of human breast (T47D), colorectal (HCT15), and cervix (HeLa) cancer cells. Except compound 11, all of the tested compounds displayed selective topo IIα inhibitory activity...
February 22, 2018: Bioorganic & Medicinal Chemistry
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