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Younghoon Kim, Xianyu Wen, Jeong Mo Bae, Jung Ho Kim, Nam-Yun Cho, Gyeong Hoon Kang
The role of tumor-associated macrophages (TAMs) in colorectal cancer (CRC) remains elusive. In this study, we aimed to examine the correlation between TAMs, clinicopathological features, tumor-infiltrating lymphocytes (TILs), and prognosis in CRC via image analysis. Immunohistochemical staining for CD68 and CD163 was performed with pan-macrophage and M2-macrophage markers, respectively. Each marker was separately analyzed for intraepithelial and stromal area densities. All four macrophage densities showed a significant correlation with one another (p = 0...
June 15, 2018: Histopathology
Qiuping Xu, Jie Shao, Shu Su, Jia Wei, Fangjun Chen, Fanyan Meng, Yang Zhao, Juan Du, Zhengyun Zou, Xiaoping Qian, Baorui Liu
Adoptive cell therapy (ACT) of autologous tumor-infiltrating lymphocytes (TILs) has shown an effect on mediating tumor regression in some patients with highly advanced, refractory metastatic malignancy. Here, the in vitro generation of TILs isolated from malignant pleural effusion and ascites was compared with which using engineered cells for costimulatory enhancement (ECCE) and 3 common γ-chain cytokines, interleukin (IL)-2, IL-7, and IL-15, alone or in combination. We showed the robust clinical-scale production of TILs with a less differentiated 'young' phenotype by expansion in the presence of ECCE combined with IL-2/7/15...
April 17, 2018: Cellular Immunology
Tsuyoshi Hamada, Thing Rinda Soong, Yohei Masugi, Keisuke Kosumi, Jonathan A Nowak, Annacarolina da Silva, Xinmeng Jasmine Mu, Tyler S Twombly, Hideo Koh, Juhong Yang, Mingyang Song, Li Liu, Mancang Gu, Yan Shi, Katsuhiko Nosho, Teppei Morikawa, Kentaro Inamura, Sachet A Shukla, Catherine J Wu, Levi A Garraway, Xuehong Zhang, Kana Wu, Jeffrey A Meyerhardt, Andrew T Chan, Jonathan N Glickman, Scott J Rodig, Gordon J Freeman, Charles S Fuchs, Reiko Nishihara, Marios Giannakis, Shuji Ogino
Inhibitors targeting the PDCD1 (programmed cell death 1, PD-1) immune checkpoint pathway have revolutionized cancer treatment strategies. The TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 ( PDCD1 ligand 1, PD-L1) expression and tumor-infiltrating lymphocytes (TIL) has been proposed to predict response to immunotherapy. It remains to be determined clinical, pathological, and molecular features of TIME subtypes of colorectal cancer. Using 812 colon and rectal carcinoma cases from the Nurses' Health Study and Health Professionals Follow-up Study, we examined the association of tumor characteristics and survival outcomes with four TIME subtypes (TIME 1, CD274 low /TILabsent ; TIME 2, CD274 high /TILpresent ; TIME 3, CD274 low /TILpresent ; and TIME 4, CD274 high /TILabsent )...
2018: Oncoimmunology
Melek Karakurt Eryilmaz, Hasan Mutlu, Betül Ünal, Derya Kıvrak Salim, Fatma Yalçın Musri, Hasan Şenol Coşkun
Objective: Increased tumor-infiltrating lymphocytes (TILs) in breast carcinoma tissues is an independent predictive factor for pathologic complete response (pCR). The increased intratumoral and stromal TILs (sTILs) in breast cancer (BC) have significant prognostic effects. In this study, we evaluated whether pCR rates to neoadjuvant chemotherapy (NACT) are higher in tumors with increased number of TILs in the pretreatment biopsy. Materials and Methods: We retrospectively evaluated the number of TILs in intratumoral TILs (iTILs) and sTILs compartments from pretreatment full-face hematoxylin and eosin-stained sections of 62 patients with locally advanced BC (LABC) who received NACT...
April 2018: Journal of Cancer Research and Therapeutics
Pål Øian, Olaug Margrete Askeland, Inger Elise Engelund, Brit Roland, Marta Ebbing
BAKGRUNN: Fødestuene utgjør en del av en differensiert og desentralisert fødselsomsorg i Norge. Hensikten med studien var å undersøke forekomst og karakteristika ved planlagte og ikke-planlagte fødestuefødsler og årsaker til overflytting samt resultater for mor og barn. MATERIALE OG METODE: I perioden 2008-10 ble et tilleggsskjema til rutinemeldingen til Medisinsk fødselsregister fortløpende utfylt av jordmor for 2 514 av i alt 2 556 (98,4 %) fødestuefødsler og for 220 fødsler som var planlagt i fødestue, men der fødselen foregikk andre steder...
June 12, 2018: Tidsskrift for Den Norske Lægeforening: Tidsskrift for Praktisk Medicin, Ny Række
Yumi A Kojima, Xiaohong Wang, Hongxia Sun, Frances Compton, Michael Covinsky, Songlin Zhang
Tumor infiltrating lymphocytes (TILs) in breast cancer play an important role in predicting the outcome of breast cancer. The goal of our current study is to investigate the consistency and reproducibility of the recommendations published by the International TILs Working Group 2014 among pathology trainees and pathologists. Hematoxylin & Eosin (H&E) slides from 129 breast cancer cases (one slide each) from 2009 to 2014 were evaluated. Each case was blindly and independently reviewed by two observers following the International TILs Working Group 2014 recommendations...
May 31, 2018: Annals of Diagnostic Pathology
Xinhong Pei, Xinxing Wang, Huixiang Li
OBJECTIVE: To investigate the mechanism of lncRNA SNHG1 in the immune escape of breast cancer (BC). METHODS: SNHG1, miR-448 and IL-10 levels were evaluated by qRT-PCR. The protein levels of IDO and Foxp3 were measured by Western blot. SNHG1 and miR-448 interaction was tested by RIP assay and RNA pull-down assay. MiR-448 and IDO interaction was observed by luciferase reporter assay. RESULTS: Compared with CD4+ T cells, miR-448 expression in CD4+ TIL cells was decreased, while the expression of SNHG1, IDO, IL-10 and Foxp3 were increased...
June 7, 2018: International Journal of Biological Macromolecules
Du Yunxia, Zhang Wei, Liu Shuxia, Feng Xiaojuan, Gao Fan, Liu Qingjuan
It is high incidence of tubulointerstitial lesion (TIL) in lupus nephritis (LN) and TIL can affect the prognosis of patients with LN. Signal transducer and activator of transcription (STAT) 3 was activated in LN and STAT3 inhibition could delay the onset of LN. Here, we evaluated the role of a well-known STAT3 inhibitor, S3I-201, on TIL in lupus nephritis. STAT3 was activated in MRL/lpr mice (a mouse model of lupus nephritis), and treatment with S3I-201 inhibited the activation of it. The level of 24-h urine protein and nitrogen urea increased in MRL/lpr mice and adminstration of S3I-201 reduced the level of urinary protein...
June 7, 2018: Biochemical and Biophysical Research Communications
Mehrdad Rakaee, Thomas K Kilvaer, Stig Manfred Dalen, Elin Richardsen, Erna-Elise Paulsen, Sigurd M Hald, Samer Al-Saad, Sigve Andersen, Tom Donnem, Roy M Bremnes, Lill-Tove Busund
The presence of tumor-infiltrating lymphocytes (TILs) positively impacts the outcome of non-small cell lung cancer (NSCLC) patients. Most previous studies have assessed TILs using different immunohistochemical assays. The purpose of this study was to develop and validate a histopathological scoring model for the assessment of TILs in whole tissue hematoxylin and eosin (H&E)-stained section slides of NSCLC patients and to evaluate the model in an immunoscore setting. Therefore, TIL was evaluated manually on H&E slides from 537 surgical specimens of primary resected stage I-III NSCLC patients...
June 6, 2018: Human Pathology
Lin Zhang, Xiaohong I Wang, Songlin Zhang
Triple-negative breast cancer (TNBC) has an aggressive behavior, limited therapeutic options, and high mortality rate. Neoadjuvant chemotherapy (NACT) is a standard treatment for TNBC and patients with pathological complete response (pCR) have a favorable outcome. We conducted a comprehensive evaluation of cancer clinicopathologic parameters, and correlated these parameters with the pCR rate and the overall survival. Fifty-eight patients with TNBC of no special type who underwent breast biopsy, neoadjuvant therapy, and mastectomy in our institution during 2005-2016 were included in this study...
June 5, 2018: Human Pathology
Azfar Neyaz, Nuzhat Husain, Swati Kumari, Sameer Gupta, Saumya Shukla, Sanya Arshad, Nidhi Anand, Arun Chaturvedi
INTRODUCTION: Gallbladder carcinoma has limited therapeutic options and a poor outcome with conventional therapy. Program death ligand (PD-L1) has been used as a potential target for immune checkpoint inhibitors in various solid neoplasms. PD-L1 expression has been studied in very few cases of gallbladder cancer. MATERIALS AND METHODS: 174 cases of gallbladder carcinoma were evaluated for PD-L1 expression using SP263 clone in tissue microarray. Clinico-pathological characteristics and survival data were correlated with PD-L1 expression analysed at different cut-offs of ≥1%, ≥10% and ≥50% in tumour cells and tumour infiltrating lymphocytes (TILs)...
June 8, 2018: Histopathology
Qian-Kun Xie, Wen-Zhuo He, Wan-Ming Hu, Lin Yang, Chang Jiang, Peng-Fei Kong, Yuan-Zhong Yang, Qiong Yang, Hui-Zhong Zhang, Bei Zhang, Liang-Ping Xia
Background: Although tumor-infiltrating lymphocytes (TILs) have been understood for years as a favorable prognostic factor for colorectal cancers (CRCs) after complete surgical resection, its prognostic role in metastatic CRC (mCRC) remains poorly defined, and it is largely unknown how this prognostic benefit relates to the metastatic status and operation modality. Materials and methods: After reviewing 2215 consecutive cases of surgically resected CRC, 332 patients newly diagnosed with stage IV CRC and treated at the Sun Yat-Sen University Cancer Center between 2009 and 2014 were included...
2018: Cancer Management and Research
Kostandinos Sideras, Boris Galjart, Angela Vasaturo, Alexander Pedroza-Gonzalez, Katharina Biermann, Shanta Mancham, Alex L Nigg, Bettina E Hansen, Hans A Stoop, Guoying Zhou, Cornelis Verhoef, Stefan Sleijfer, Dave Sprengers, Jaap Kwekkeboom, Marco J Bruno
BACKGROUND AND OBJECTIVES: Patients with isolated colorectal-cancer-liver-metastases (CRCLM) frequently undergo metastatectomy. Tumor-infiltrating-lymphocytes (TILs) have prognostic potential in the setting of primary colorectal cancer, however, their role in CRCLM is less studied. We aimed to study the spatial distribution and prognostic role of tumor-infiltrating CD8+ cytotoxic T-cells and FoxP3+ regulatory T-cells at the metastatic site of CRCLM patients. METHODS: TILs were isolated from fresh metastatic tissues of 47 patients with CRCLM...
June 7, 2018: Journal of Surgical Oncology
Ying Ying Tang, Si Yuan Sheng, Chuan Gang Lu, Yu Qing Zhang, Jian Yong Zou, Yi Yan Lei, Yong Gu, Hai Hong
The canonical Wnt-β-catenin signaling pathway arrests the differentiation of T cells and plays an important role in phenotypic maintenance of naive T cells and stem cell-like memory T cells in human peripheral blood, but its effect on tumor-infiltrating lymphocytes (TILs) from non-small cell lung cancer is little known. In this study, we showed that glycogen synthase kinase-3β inhibitor TWS119 has different effects on CD4 and CD8 T cells in TILs. TWS119 preserved the expansion of naive T cell and CD8 stem cell-like memory T cells, and induced CD8 effector T-cell proliferation in TILs...
June 5, 2018: Journal of Immunotherapy
Montika Bush, Ross J Simpson, Anna Kucharska-Newton, Gang Fang, Til Stürmer, M Alan Brookhart
BACKGROUND: Studies of the use of health care after the onset of disease are important for assessing quality of care, treatment disparities, and guideline compliance. Cohort definition and analysis method are important considerations for the generalizability and validity of study results. We compared different approaches for cohort definition (restriction by survival time vs. comorbidity score) and analysis method [Kaplan-Meier (KM) vs. competing risk] when assessing patterns of guideline adoption in elderly patients...
June 5, 2018: Medical Care
Dagmar Kollmann, Desislava Ignatova, Julia Jedamzik, Yun-Tsan Chang, Gerd Jomrich, Andreas Baierl, Dmitry Kazakov, Michal Michal, Lars E French, Wolfram Hoetzenecker, Tobias Schatton, Reza Asari, Matthias Preusser, Michael Gnant, Emmanuella Guenova, Sebastian F Schoppmann
Background . The outcome of patients with adenocarcinoma of the esophagogastric junction (AEG) remains poor. The programmed cell-death-protein-1 (PD-1), a co-inhibitory receptor primarily expressed by T-cells, represents a potential new therapeutic target. PD-1, PD-1 ligand 1 (PD-L1), and PD-L2 expression have all been described as prognostic factors in a variety of cancers. Their expression patterns in AEG, however, are poorly understood. We analyzed PD-L1, PD-L2 and PD-1 expression by tumor-infiltrating lymphocytes (TILs) and cancer-cells in tumor-biospecimens in AEG-patients...
2018: Oncoimmunology
Yoon Jin Cha, Sung Gwe Ahn, Soong June Bae, Chang Ik Yoon, Jayeong Seo, Woo Hee Jung, Eun Ju Son, Joon Jeong
PURPOSE: Neoadjuvant chemotherapy (NAC) is being increasingly used to treat locally advanced breast cancer and to conserve the breast. In triple-negative breast cancer and HER2-positive breast cancer, a high density of tumor-infiltrating lymphocytes (TILs) is an important predictor of NAC response. Thus far, it remains unclear whether the TIL scores in core needle biopsies (CNBs) are closely representative of those in the whole tumor section in resected specimens. This study aimed to evaluate the concordance between the TIL scores of CNBs and resected specimens of breast cancer...
June 5, 2018: Breast Cancer Research and Treatment
Annelisa M Cornel, Niek P van Til, Jaap Jan Boelens, Stefan Nierkens
Dendritic cell (DC) vaccination has been investigated as a potential strategy to target hematologic malignancies, while generating sustained immunological responses to control potential future relapse. Nonetheless, few clinical trials have shown robust long-term efficacy. It has been suggested that a combination of surmountable shortcomings, such as selection of utilized DC subsets, DC loading and maturation strategies, as well as tumor-induced immunosuppression may be targeted to maximize anti-tumor responses of DC vaccines...
2018: Frontiers in Immunology
Nikolaos Zacharakis, Harshini Chinnasamy, Mary Black, Hui Xu, Yong-Chen Lu, Zhili Zheng, Anna Pasetto, Michelle Langhan, Thomas Shelton, Todd Prickett, Jared Gartner, Li Jia, Katarzyna Trebska-McGowan, Robert P Somerville, Paul F Robbins, Steven A Rosenberg, Stephanie L Goff, Steven A Feldman
Immunotherapy using either checkpoint blockade or the adoptive transfer of antitumor lymphocytes has shown effectiveness in treating cancers with high levels of somatic mutations-such as melanoma, smoking-induced lung cancers and bladder cancer-with little effect in other common epithelial cancers that have lower mutation rates, such as those arising in the gastrointestinal tract, breast and ovary1-7 . Adoptive transfer of autologous lymphocytes that specifically target proteins encoded by somatically mutated genes has mediated substantial objective clinical regressions in patients with metastatic bile duct, colon and cervical cancers8-11 ...
June 2018: Nature Medicine
Patrick J McIntire, Lina Irshaid, Yifang Liu, Zhengming Chen, Faith Menken, Eugene Nowak, Sandra J Shin, Paula S Ginter
BACKGROUND: CD8+ tumor-infiltrating lymphocytes (TILs) have emerged as a prognostic indicator in triple-negative breast cancer (TNBC). There is debate surrounding the prognostic value of hot spots for CD8+ TIL enumeration. METHODS: We compared hot spot versus whole-tumor CD8+ TIL enumeration in prognosticating TNBC using immunohistochemistry on whole tissue sections and quantification by digital image analysis (Halo imaging analysis software; Indica Labs, Corrales, NM)...
May 7, 2018: Clinical Breast Cancer
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