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Tumor infiltrating lymphocyte

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https://www.readbyqxmd.com/read/28448494/integrin-%C3%AE-1-activation-induces-an-anti-melanoma-host-response
#1
Laila Ritsma, Ipsita Dey-Guha, Nilesh Talele, Xavier Sole, Salony, Joeeta Chowdhury, Kenneth N Ross, Sridhar Ramaswamy
TGF-β is a cytokine thought to function as a tumor promoter in advanced malignancies. In this setting, TGF-β increases cancer cell proliferation, survival, and migration, and orchestrates complex, pro-tumorigenic changes in the tumor microenvironment. Here, we find that in melanoma, integrin β1-mediated TGF-β activation may also produce tumor suppression via an altered host response. In the A375 human melanoma cell nu/nu xenograft model, we demonstrate that cell surface integrin β1-activation increases TGF-β activity, resulting in stromal activation, neo-angiogenesis and, unexpectedly for this nude mouse model, increase in the number of intra-tumoral CD8+ T lymphocytes within the tumor microenvironment...
2017: PloS One
https://www.readbyqxmd.com/read/28447277/assessment-of-pd-1-positive-cells-on-initial-and-secondary-resected-tumor-specimens-of-newly-diagnosed-glioblastoma-and-its-implications-on-patient-outcome
#2
Tsubasa Miyazaki, Eiichi Ishikawa, Masahide Matsuda, Hiroyoshi Akutsu, Satoru Osuka, Noriaki Sakamoto, Shingo Takano, Tetsuya Yamamoto, Koji Tsuboi, Akira Matsumura
Glioblastoma (GBM) is the most common type of malignant brain tumor and has a very poor prognosis. Most patients relapse within 12 months despite aggressive treatment and patient outcome after recurrent is extremely worse. This study was designed to clarify the change of the molecular expression, including programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), on the initial and secondary resected tumor specimens and to address the influence of these expressions for patient outcome after second surgery of glioblastoma...
April 26, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28445952/socs3-inhibits-the-pathological-effects-of-il-22-in-non-melanoma-skin-tumor-derived-keratinocytes
#3
Stefania Madonna, Claudia Scarponi, Martina Morelli, Rosanna Sestito, Pasqualina Liana Scognamiglio, Daniela Marasco, Cristina Albanesi
Basal cell carcinomas (BCC) and squamous-cell carcinomas (SCC) are common malignancies in humans, caused by neoplastic transformation of keratinocytes of the basal or suprabasal layers of epidermis, respectively. Tumor-infiltrating lymphocytes (TILs) are frequently found in BCC and SCC, and functionally promote epithelial carcinogenesis. TILs secreting IL-22, in particular, participate to BCC and SCC growth by inducing keratinocyte proliferation and migration, as well as the expression of inflammatory, anti-apoptotic and pro-angiogenic genes...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445951/pd-l1-expression-in-perihilar-and-intrahepatic-cholangiocarcinoma
#4
Jacqueline Fontugne, Jérémy Augustin, Anaïs Pujals, Philippe Compagnon, Benoit Rousseau, Alain Luciani, Christophe Tournigand, Daniel Cherqui, Daniel Azoulay, Jean-Michel Pawlotsky, Julien Calderaro
Cholangiocarcinoma is an aggressive biliary neoplasm lacking effective therapeutic agents. Immunotherapies targeting the PD-L1/PD-1 immune checkpoint have shown encouraging results in solid and hematologic cancers in clinical trials. Response to these immunomodulators is correlated with PD-L1 expression. Our goal was to characterize PD-L1 expression in intra-hepatic (iCCA) and perihilar (pCCA) cholangiocarcinomas, and to correlate our results with clinicopathological features, density of tumor-infiltrating lymphocytes (TILs) and PD-1 expression...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443470/a-multi-target-protein-of-htertr-fam96a-presents-significant-anticancer-potent-in-the-treatment-of-hepatocellular-carcinoma
#5
Meng-Yu Zhang, Jie-Ping Wang
The abilities to escape apoptosis induced by anticancer drugs are an essential factor of carcinogenesis and a hallmark of resistance to cancer therapy. In this study, we identified hTERTR-FAM96A (human telomerase reverse transcriptase-family with sequence similarity 96 member A) as a new efficient agent for apoptosome-activating and anti-tumor protein and investigated the potential tumor suppressor function in hepatocellular carcinoma. The hTERTR-FAM96A fusion protein was constructed by genetic engineering and its anticancer function of hTERTR-FAM96A was explored in vitro and in vivo by investigating the possible preclinical outcomes...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28441526/it-s-t-time-for-normal-blood-vessels
#6
Bernard Thienpont, Diether Lambrechts
In a new report in Nature, Tian and colleagues (2017) describe that T cell activation in tumors induces blood vessel normalization. Because abnormal vasculature in tumors is known to reduce chemotherapy effectiveness and T lymphocyte infiltration and to increase metastasis, this suggests an exciting novel angle for checkpoint immunotherapy.
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28438506/diacylglycerol-kinase-%C3%AE-limits-cytokine-dependent-expansion-of-cd8-t-cells-with-broad-antitumor-capacity
#7
Elena Andrada, Rosa Liébana, Isabel Merida
Interleukin-2 and -15 drive expansion/differentiation of cytotoxic CD8(+) T cells that eliminate targets via antigen-independent killing. This property is clinically relevant for the improvement of T cell-based antitumor therapies. Diacylglycerol kinase α and ζ (DGKα/ζ) metabolize the diacylglycerol generated following antigen recognition by T lymphocytes. Enhanced expression of these two lipid kinases in tumor-infiltrating CD8(+) T cells promotes a hyporesponsive state that contributes to tumor immune escape...
April 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28433635/prognostic-significance-and-functional-implication-of-immune-activating-receptor-nkg2d-in-gastric-cancer
#8
Fengjuan Lin, Congqi Dai, Xiaoxiao Ge, Wenbo Tang, Ying Lin, Yan Wang, Jin Li
NKG2D, an activating receptor expressed on CD8(+) T lymphocytes, serves as a co-stimulation molecule by engagement with its ligands MICA/B and ULBPs to trigger immune activation against tumors. Currently, the biological function and clinical significance of NKG2D in gastric cancer remains unexplored. The study aims to investigate the expression of NKG2D in gastric cancer in association with clinical prognosis and its biological function. Real-time PCR was used to analyze NKG2D expression in paired cancer and adjacent non-malignant tissues in 139 gastric cancer patients between 2007 and 2010 in Shanghai Cancer Center...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28432397/downregulation-of-neuropilin-1-on-macrophages-modulates-antibody-mediated-tumoricidal-activity
#9
Kosuke Kawaguchi, Eiji Suzuki, Mariko Nishie, Isao Kii, Tatsuki R Kataoka, Masahiro Hirata, Masashi Inoue, Fengling Pu, Keiko Iwaisako, Moe Tsuda, Ayane Yamaguchi, Hironori Haga, Masatoshi Hagiwara, Masakazu Toi
Neuropilin-1 (NRP-1)-expressing macrophages are engaged in antitumor immune functions via various mechanisms. In this study, we investigated the role of NRP-1 on macrophages in antibody-mediated tumoricidal activity. Treatment of macrophages with NRP-1 knockdown or an anti-NRP-1-neutralizing antibody significantly suppressed antibody-dependent cellular cytotoxicity and modulated cytokine secretion from macrophages in vitro. Furthermore, in vivo studies using a humanized mouse model bearing human epidermal growth factor receptor-2 (HER2)-positive breast cancer xenografts showed that antibody-mediated antitumor activity and tumor infiltration of CD4(+) T lymphocytes were significantly downregulated when peripheral blood mononuclear cells in which NRP-1 was knocked down were co-administered with an anti-HER2 antibody...
April 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28430349/prognostic-significance-of-infiltrating-immune-cell-subtypes-in-invasive-ductal-carcinoma-of-the-breast
#10
Yangmei Xu, Suzhen Lan, Qiuhong Zheng
PURPOSE: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis. MATERIALS AND METHODS: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low)...
April 20, 2017: Tumori
https://www.readbyqxmd.com/read/28429196/expression-of-programmed-cell-death-protein-1-by-tumor-infiltrating-lymphocytes-and-tumor-cells-is-associated-with-advanced-tumor-stage-in-patients-with-esophageal-adenocarcinoma
#11
Dagmar Kollmann, Desislava Ignatova, Julia Jedamzik, Yun-Tsan Chang, Gerd Jomrich, Matthias Paireder, Ivan Kristo, Dmitry Kazakov, Michal Michal, Antonio Cozzio, Wolfram Hoetzenecker, Tobias Schatton, Reza Asari, Matthias Preusser, Emmanuella Guenova, Sebastian F Schoppmann
BACKGROUND: Despite recent advances in the therapy for adenocarcinoma of the esophagogastric junction (AEG), overall prognosis remains poor. Programmed cell death protein 1 (PD1) is a co-inhibitory receptor primarily expressed by T-cells. Tumor cells can escape anticancer immune responses by triggering the PD1 pathway. Moreover, PD1 receptor engagement on cancer cells may trigger tumor-intrinsic growth signals. This study aimed to evaluate the potential clinical relevance of PD1 expression by tumor-infiltrating lymphocytes (TILs) and cancer cells in the AEG...
April 20, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28428277/immune-gene-expression-is-associated-with-genomic-aberrations-in-breast-cancer
#12
Anton Safonov, Tingting Jiang, Giampaolo Bianchini, Balázs Győrffy, Thomas Karn, Christos Hatzis, Lajos Pusztai
The presence of tumor-infiltrating lymphocytes (TIL) is a favorable prognostic factor in breast cancer, but what drives immune infiltration remains unknown. Here we examine if clonal heterogeneity, total mutation load, neoantigen load, copy number variations (CNV), gene- or pathway-level somatic mutations, or germline polymorphisms (SNP) are associated with immune metagene expression in breast cancer subtypes. Thirteen published immune metagenes correlated separately with genomic metrics in the 3 major breast cancer subtypes...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428066/effects-of-gold-nanoparticle-based-vaccine-size-on-lymph-node-delivery-and-cytotoxic-t-lymphocyte-responses
#13
Sukmo Kang, Sukyung Ahn, Jeewon Lee, Jin Yong Kim, Minsuk Choi, Vipul Gujrati, Hyungjun Kim, Jinjoo Kim, Eui-Cheol Shin, Sangyong Jon
Although it has been shown that the size of nanoparticle-based vaccines is a key determining factor for the induction of immune responses, few studies have provided detailed analyses of thresholds or critical sizes of nanoparticle vaccines. Here we report effects of the size of gold nanoparticle (GNP)-based vaccines on their efficiency of delivery to lymph nodes (LNs) and induction of CD8(+) T-cell responses. We further propose a threshold size of GNPs for use as an effective vaccine. To examine the effects of GNP size, we synthesized GNPs with diameters of 7, 14 and 28nm, and then conjugated them with recombinant ovalbumin (OVA) as a model antigen...
April 18, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28427171/evaluation-of-intracavitary-administration-of-curcumin-for-the-treatment-of-sarcomatoid-mesothelioma
#14
Daniel L Pouliquen, Béatrice Nawrocki-Raby, Joëlle Nader, Stéphanie Blandin, Myriam Robard, Philippe Birembaut, Marc Grégoire
A rat model of sarcomatoid mesothelioma, mimicking some of the worst clinical conditions encountered, was established to evaluate the therapeutic potential of intracavitary curcumin administration.The M5-T1 cell line, selected from a collection established from F344 rats induced with asbestos, produces tumors within three weeks, with extended metastasis in normal tissues, after intraperitoneal inoculation in syngeneic rats. The optimal concentration/time conditions for killing M5-T1 cells with curcumin were first determined in vitro...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426105/the-prevalence-and-clinical-relevance-of-tumor-infiltrating-lymphocytes-tils-in-ductal-carcinoma-in-situ-of-the-breast
#15
G Pruneri, M Lazzeroni, V Bagnardi, G B Tiburzio, N Rotmensz, A DeCensi, A Guerrieri-Gonzaga, A Vingiani, G Curigliano, S Zurrida, F Bassi, R Salgado, G Van den Eynden, S Loi, C Denkert, B Bonanni, G Viale
Background: Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct in invasive breast cancer, but their clinical role in ductal carcinoma in situ (DCIS) has not been ascertained. Patients and methods: We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women with a median follow-up of 8.2 years. Detailed criteria for TILs evaluation were pre-defined involving the International Immuno-Oncology Biomarker Working Group...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28425129/role-of-sialyl-6-sulfo-lewis-x-in-anti-tumor-immunity-against-oral-squamous-cell-carcinoma
#16
Hisato Yoshida, Hitomi Hoshino, Yoshiaki Imamura, Hitoshi Yoshimura, Kazuo Sano, Motohiro Kobayashi
BACKGROUND: Tumor-infiltrating lymphocytes (TILs) reportedly play a pivotal role in anti-tumor immunity against oral squamous cell carcinoma (OSCC); however, mechanisms governing TIL recruitment to OSCC tissues remain to be clarified. The present study was undertaken to assess a potential association between TILs and high endothelial venule (HEV)-like vessels that express sialyl 6-sulfo Lewis X (LeX). METHODS: OSCC tissue sections (n = 41) were subjected to immunohistochemistry for sialyl 6-sulfo LeX and CD34 to allow quantitation of HEV-like vessels...
April 20, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28424660/ccl2-monocyte-chemoattractant-protein-1-and-parathyroid-hormone-action-on-bone
#17
REVIEW
Jawed Akhtar Siddiqui, Nicola C Partridge
Chemokines are small molecules that play a crucial role as chemoattractants for several cell types, and their components are associated with host immune responses and repair mechanisms. Chemokines selectively recruit monocytes, neutrophils, and lymphocytes and induce chemotaxis through the activation of G protein-coupled receptors. Two well-described chemokine families (CXC and CC) are known to regulate the localization and trafficking of immune cells in cases of injury, infection, and tumors. Monocyte chemoattractant protein 1 (MCP-1/CCL2) is one of the important chemokines from the CC family that controls migration and infiltration of monocytes/macrophages during inflammation...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28423678/influence-of-ipilimumab-on-expanded-tumour-derived-t-cells-from-patients-with-metastatic-melanoma
#18
Jon Bjoern, Rikke Lyngaa, Rikke Andersen, Lisbet Hölmich Rosenkrantz, Sine Reker Hadrup, Marco Donia, Inge Marie Svane
INTRODUCTION: Tumour infiltrating lymphocyte (TIL) based adoptive cell therapy (ACT) is a promising treatment for patients with advanced melanoma. Retrospective studies suggested an association between previous treatment with anti-CTLA-4 antibodies and long term survival after subsequent ACT. Thus, we hypothesized that treatment with anti-CTLA-4 antibodies can induce favourable changes to be detected in TILs. RESULTS: Expanded T cells from Ipilimumab treated patients had a higher proportion of cells expressing CD27, intracellular CTLA-4, TIM-3 and LAG-3...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423548/axl-acts-as-a-tumor-suppressor-by-regulating-light-expression-in-t-lymphoma
#19
Eun-Hee Lee, Eun-Mi Kim, Kon-Young Ji, A-Reum Park, Ha-Rim Choi, Hwa-Youn Lee, Su-Man Kim, Byung Yeoup Chung, Chul-Hong Park, Hyo Jin Choi, Young-Hyeh Ko, Hyoung-Woo Bai, Hyung-Sik Kang
Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT expression was upregulated through activation of the PI3K/AKT signaling pathway and transcriptional induction by Sp1...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423520/prognostic-role-of-programmed-death-ligand-1-pd-l1-expressing-tumor-infiltrating-lymphocytes-in-testicular-germ-cell-tumors
#20
Michal Chovanec, Zuzana Cierna, Viera Miskovska, Katarina Machalekova, Daniela Svetlovska, Katarina Kalavska, Katarina Rejlekova, Stanislav Spanik, Karol Kajo, Pavel Babal, Jozef Mardiak, Michal Mego
PURPOSE: Testicular germ cell tumors (TGCTs) are nearly universally curable malignancies. Nevertheless, standard cisplatin-based chemotherapy is not curative in a small subgroup of patients. Previously, we showed that PD-L1 overexpression is associated with worse prognosis in TGCTs, while tumor infiltrating lymphocytes (TILs) are prognostic in different types of cancer. This study aimed to evaluate the prognostic value of PD-1 and PD-L1 expressing TILs in TGCTs. RESULTS: PD-L1 positive TILs were found significantly more often in seminomas (95...
March 28, 2017: Oncotarget
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