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https://www.readbyqxmd.com/read/29770915/cytolytic-activity-score-to-assess-anticancer-immunity-in-colorectal-cancer
#1
Sumana Narayanan, Tsutomu Kawaguchi, Li Yan, Xuan Peng, Qianya Qi, Kazuaki Takabe
BACKGROUND: Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. METHODS: Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29747685/car-t-cell-therapy-for-breast-cancer-harnessing-the-tumor-milieu-to-drive-t-cell-activation
#2
Pradip Bajgain, Supannikar Tawinwung, Lindsey D'Elia, Sujita Sukumaran, Norihiro Watanabe, Valentina Hoyos, Premal Lulla, Malcolm K Brenner, Ann M Leen, Juan F Vera
BACKGROUND: The adoptive transfer of T cells redirected to tumor via chimeric antigen receptors (CARs) has produced clinical benefits for the treatment of hematologic diseases. To extend this approach to breast cancer, we generated CAR T cells directed against mucin1 (MUC1), an aberrantly glycosylated neoantigen that is overexpressed by malignant cells and whose expression has been correlated with poor prognosis. Furthermore, to protect our tumor-targeted cells from the elevated levels of immune-inhibitory cytokines present in the tumor milieu, we co-expressed an inverted cytokine receptor linking the IL4 receptor exodomain with the IL7 receptor endodomain (4/7ICR) in order to transform the suppressive IL4 signal into one that would enhance the anti-tumor effects of our CAR T cells at the tumor site...
May 10, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29732570/cd206-positive-myeloid-cells-bind-galectin-9-and-promote-a-tumor-supportive-microenvironment
#3
Elizabeth Ann L Enninga, Kyriakos Chatzopoulos, John T Butterfield, Shari L Sutor, Alexey A Leontovich, Wendy K Nevala, Thomas J Flotte, Svetomir N Markovic
In patients with metastatic melanoma, high blood levels of galectin-9 are correlated with worse overall survival and a bias towards a Th2 inflammatory state supportive of tumor growth. Although galectin-9 signaling through TIM3 on T cells has been described, less is known about the interaction of galectin-9 with macrophages. We aimed to determine whether galectin-9 is a binding partner of CD206 on macrophages and whether the result of this interaction is tumor-supportive. It was determined that incubation of CD68+ macrophages with galectin-9 or anti-CD206 blocked target binding and that both CD206 and galectin-9 were detected by immunoprecipitation of cell lysates...
May 7, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29706626/long-non-coding-rna-lnc-tim3-exacerbates-cd8-t-cell-exhaustion-via-binding-to-tim-3-and-inducing-nuclear-translocation-of-bat3-in-hcc
#4
Jie Ji, Yin Yin, Huanyu Ju, Xiaoliang Xu, Wei Liu, Qiang Fu, Jiaojiao Hu, Xudong Zhang, Beicheng Sun
Although one of the first comprehensive examinations of long non-coding RNA (lncRNA) expression was performed in human CD8 T lymphocytes, little is known about their roles in CD8 T cells functions during the progression of hepatocellular carcinoma (HCC). Here, we show that Lnc-Tim3 is upregulated and negatively correlates with IFN-γ and IL-2 production in tumor-infiltrating CD8 T cells of HCC patients. Lnc-Tim3 plays a pivotal role in stimulating CD8 T exhaustion and the survival of the exhausted CD8 T cells...
April 30, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29665497/the-effects-of-resiquimod-in-an-ovalbumin-induced-allergic-rhinitis-model
#5
Shenhong Qu, Taijie Qin, Min Li, Shaojie Zhang, Linsong Ye, Jiazhang Wei, Hua Fan, Baiwen Chen
Growing evidence indicates that the Toll-like receptor7/8(TLR7/8) agonist resiquimod (R848) is a potential inhibitor of type-2 immunity. However, the mechanisms mediating its therapeutic effects are not fully understood. This study investigated the effects of R848 on OVA-induced allergic rhinitis(AR) mice and the expression of IL-25, IL-33, TSLP, T-cell immunoglobulin mucin1 (TIM1) and T-cell immunoglobulin mucin3 (TIM3). BALB/c mice were intranasally sensitized and challenged with ovalbumin (OVA), and R848 was intraperitoneally injected into AR mice...
April 14, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29544815/cd8-cxcr5-t-cells-in-tumor-draining-lymph-nodes-are-highly-activated-and-predict-better-prognosis-in-colorectal-cancer
#6
Jifu E, Feihu Yan, Zhengchun Kang, Liangliang Zhu, Junjie Xing, Enda Yu
Tumor-draining lymph nodes (TDLNs) are the primary sites of tumor antigen presentation, as well as the origin of metastasis in most cases. Hence, the type and function of immune cells in TDLNs are critical to the microenvironment and potentially affect the clinical outcome of the malignancy. CD8+ CXCR5+ T cells are recently described to present high effector functions in infectious diseases, but their role in colorectal cancer (CRC) remains unclear. In forty-four Stage III CRC patients, we examined the CD8+ CXCR5+ T cells in blood, tumor, and TDLN...
March 12, 2018: Human Immunology
https://www.readbyqxmd.com/read/29526824/immunohistochemical-and-image-analysis-based-study-demonstrate-that-several-immune-checkpoints-are-co-expressed-in-non-small-cell-lung-carcinoma-tumors
#7
Edwin Roger Parra, Pamela Villalobos, Jiexin Zhang, Carmen Behrens, Barbara Mino, Stephen Swisher, Boris Sepesi, Annika Weissferdt, Neda Kalhor, John Victor Heymach, Cesar Moran, Jianjun Zhang, Jack Lee, Jaime Rodriguez-Canales, Don Gibbons, Ignacio Ivan Wistuba
BACKGROUND: The understanding of immune checkpoint molecules' co-expression in non-small cell lung carcinoma (NSCLC) is important to potentially design combinatorial immunotherapy approaches. MATERIAL AND METHODS: We studied 225 formalin-fixed, paraffin-embedded tumor tissues from stage I-III NSCLCs-142 adenocarcinomas (ADCs) and 83 squamous cell carcinomas (SCCs)-placed in tissue microarrays. Nine immune checkpoint markers were evaluated; 4 (PD-L1, B7-H3, B7-H4, and IDO-1) expressed predominantly in malignant cells (MCs) and 5 (ICOS, VISTA, TIM3, LAG3, and OX40) expressed mostly in stromal tumor-associated inflammatory cells (TAICs)...
March 8, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29518102/expression-of-pd-1-and-tim-3-markers-of-t-cell-exhaustion-is-associated-with-cd4-dynamics-during-the-course-of-untreated-and-treated-hiv-infection
#8
Norma Rallón, Marcial García, Javier García-Samaniego, Alfonso Cabello, Beatriz Álvarez, Clara Restrepo, Sara Nistal, Miguel Górgolas, José M Benito
INTRODUCTION: T-cell exhaustion has been involved in the pathogenesis of HIV infection. We have longitudinally analyzed PD1 and Tim3 surrogate markers of T-cells exhaustion, in parallel with other markers of HIV progression, and its potential association with CD4 changes in treated and untreated infection. PATIENTS AND METHODS: 96 HIV patients, 49 of them followed in the absence of cART (cART-naïve group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 [IQR: 31-60] months...
2018: PloS One
https://www.readbyqxmd.com/read/29506555/blockade-of-tim3-relieves-immunosuppression-through-reducing-regulatory-t-cells-in-head-and-neck-cancer
#9
Jian-Feng Liu, Lei Wu, Lei-Lei Yang, Wei-Wei Deng, Liang Mao, Hao Wu, Wen-Feng Zhang, Zhi-Jun Sun
BACKGROUND: T-cell immunoglobulin mucin 3 (TIM3) is a negative immune checkpoint and plays a crucial part in tumor-induced immune suppression. However, the mechanism of TIM3 in regulating immunosuppression in head and neck squamous cell carcinoma (HNSCC) was still not quite clear. METHODS: We carried out the immunohistochemistry staining of HNSCC tissue microarrays. Through quantification of the histoscore, we performed the correlation analysis among the TIM3, Galectin-9, Foxp3, CD68 and CD163...
March 5, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29484121/novel-mutational-landscapes-and-expression-signatures-of-lung-squamous-cell-carcinoma
#10
Donghai Xiong, Jing Pan, Yuxin Yin, Hui Jiang, Eva Szabo, Ronald A Lubet, Yian Wang, Ming You
Lung squamous cell carcinoma (LUSC) is a major subtype of Non-Small Cell Lung Cancer. To increase our understanding of the LUSC pathobiology, we performed exome sequencing and RNA-seq in 16 murine carcinogen-induced LUSC tumors and 8 normal murine lung tissue samples. Additionally, we conducted single-cell RNA-seq on two independent tumors from the same murine model. We identified a list of 59 cancer genes recurrently mutated in the mice LUSC tumors, 47 (80%) of which were also mutated in human LUSCs. At the single cell level, we detected unique clonal mutation patterns for each of the two LUSC tumors, being initiated from clones carrying the mutant Igfbp7 and Trp53 genes, respectively...
January 26, 2018: Oncotarget
https://www.readbyqxmd.com/read/29459868/characteristics-of-infection-immunity-regulated-by-toxoplasma-gondii-to-maintain-chronic-infection-in-the-brain
#11
Young Sang Hwang, Ji-Hun Shin, Jung-Pyo Yang, Bong-Kwang Jung, Sang Hyung Lee, Eun-Hee Shin
To examine the immune environment of chronic Toxoplasma gondii infection in the brain, the characteristics of infection-immunity (premunition) in infection with T . gondii strain ME49 were investigated for 12 weeks postinfection (PI). The results showed that neuronal cell death, microglia infiltration and activation, inflammatory and anti-inflammatory cytokine expression, Stat1 phosphorylation, and microglia activation and inflammatory gene transcripts related to M1 polarization in the brain were increased during the acute infection (AI) stage (within 6 weeks PI), suggesting that innate and cellular inflammatory response activation and neurodegeneration contributed to excessive inflammatory responses...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29383101/cxcr2-mdscs-promote-breast-cancer-progression-by-inducing-emt-and-activated-t-cell-exhaustion
#12
Ha Zhu, Yan Gu, Yiquan Xue, Ming Yuan, Xuetao Cao, Qiuyan Liu
Although myeloid-derived suppressor cells (MDSCs) have been demonstrated to contribute to tumor initiation, progression and metastasis, however, which MDSC subsets are preferentially expanded and activated, and what's the key molecular mechanism responsible for specific MDSC subsets in promoting tumor progression need to be fully addressed. Here we identify that Ly6Gmi Ly6Clo CD11b+ CXCR2+ subpopulation (named CXCR2+ MDSCs) are predominately expanded and recruited in systemic and local tumor microenvironment during breast cancer progression and metastasis...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29308304/pd-1-related-transcriptome-profile-and-clinical-outcome-in-diffuse-gliomas
#13
Shuai Liu, Zheng Wang, Yinyan Wang, Xing Fan, Chuanbao Zhang, Wenbin Ma, Xiaoguang Qiu, Tao Jiang
Background: PD-1 plays a critical part in control of immune response to malignancy. Anti-PD-1 treatment is a hopeful strategy to improve the dismal prognosis of gliomas. To characterize the role of PD-1 in diffuse gliomas, we investigated its related biological process at transcriptome level and its clinical prognostic value. Method and patients: Through Chinese Glioma Genome Atlas and TCGA datasets, we systematically reviewed a total of 994 cases with RNA-seq data and analyzed the functional annotation of PD-1 by Gene ontology (GO) analysis...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29230224/lipoarabinomannan-decreases-galectin-9-expression-and-tumor-necrosis-factor-pathway-in-macrophages-favoring-mycobacterium-tuberculosis-intracellular-growth
#14
Leslie Chávez-Galán, Lucero Ramon-Luing, Claudia Carranza, Irene Garcia, Isabel Sada-Ovalle
Lipoarabinomannan (LAM) is a lipid virulent factor secreted by Mycobacterium tuberculosis ( Mtb ). LAM can be found in the sputum and urine of patients with active tuberculosis. When human monocytes are differentiated into macrophages [monocyte-derived macrophages (MDM)] in the presence of LAM, MDM are poorly functional which may limit the immune response to Mtb infection. Our previous studies have shown that TIM3 and galectin (GAL)9 interaction induces anti-mycobacterial activity, and the expression levels of TIM3 and GAL9 are downregulated during Mtb infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29206680/immune-therapies-in-acute-myeloid-leukemia-a-focus-on-monoclonal-antibodies-and-immune-checkpoint-inhibitors
#15
Rita Assi, Hagop Kantarjian, Farhad Ravandi, Naval Daver
PURPOSE OF REVIEW: This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD-1). RECENT FINDINGS: The stellar success of immune therapies that harness the power of T cells in solid tumors and an improved understanding of the immune system in patients with hematologic malignancies have resulted in major efforts to develop immune therapies for the treatment of patients with AML...
March 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29184980/blockage-of-the-nlrp3-inflammasome-by-mcc950-improves-anti-tumor-immune-responses-in-head-and-neck-squamous-cell-carcinoma
#16
Lei Chen, Cong-Fa Huang, Yi-Cun Li, Wei-Wei Deng, Liang Mao, Lei Wu, Wen-Feng Zhang, Lu Zhang, Zhi-Jun Sun
The NLRP3 inflammasome is a critical innate immune pathway responsible for producing active interleukin (IL)-1β, which is associated with tumor development and immunity. However, the mechanisms regulating the inflammatory microenvironment, tumorigenesis and tumor immunity are unclear. Herein, we show that the NLRP3 inflammasome was over-expressed in human HNSCC tissues and that the IL-1β concentration was increased in the peripheral blood of HNSCC patients. Additionally, elevated NLRP3 inflammasome levels were detected in tumor tissues of Tgfbr1/Pten 2cKO HNSCC mice, and elevated IL-1β levels were detected in the peripheral blood serum, spleen, draining lymph nodes and tumor tissues...
November 28, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29163490/immune-checkpoint-molecules-on-tumor-infiltrating-lymphocytes-and-their-association-with-tertiary-lymphoid-structures-in-human-breast-cancer
#17
Cinzia Solinas, Soizic Garaud, Pushpamali De Silva, Anaïs Boisson, Gert Van den Eynden, Alexandre de Wind, Paolo Risso, Joel Rodrigues Vitória, François Richard, Edoardo Migliori, Grégory Noël, Hugues Duvillier, Ligia Craciun, Isabelle Veys, Ahmad Awada, Vincent Detours, Denis Larsimont, Martine Piccart-Gebhart, Karen Willard-Gallo
There is an exponentially growing interest in targeting immune checkpoint molecules in breast cancer (BC), particularly in the triple-negative subtype where unmet treatment needs remain. This study was designed to analyze the expression, localization, and prognostic role of PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM3 in primary BC. Gene expression analysis using the METABRIC microarray dataset found that all six immune checkpoint molecules are highly expressed in basal-like and HER2-enriched compared to the other BC molecular subtypes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29141863/eight-color-multiplex-immunohistochemistry-for-simultaneous-detection-of-multiple-immune-checkpoint-molecules-within-the-tumor-microenvironment
#18
Mark A J Gorris, Altuna Halilovic, Katrin Rabold, Anne van Duffelen, Iresha N Wickramasinghe, Dagmar Verweij, Inge M N Wortel, Johannes C Textor, I Jolanda M de Vries, Carl G Figdor
Therapies targeting immune checkpoint molecules CTLA-4 and PD-1/PD-L1 have advanced the field of cancer immunotherapy. New mAbs targeting different immune checkpoint molecules, such as TIM3, CD27, and OX40, are being developed and tested in clinical trials. To make educated decisions and design new combination treatment strategies, it is vital to learn more about coexpression of both inhibitory and stimulatory immune checkpoints on individual cells within the tumor microenvironment. Recent advances in multiple immunolabeling and multispectral imaging have enabled simultaneous analysis of more than three markers within a single formalin-fixed paraffin-embedded tissue section, with accurate cell discrimination and spatial information...
January 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29089645/identification-and-characterization-of-hla-a24-specific-xbp1-cd138-syndecan-1-and-cs1-slamf7-peptides-inducing-antigens-specific-memory-cytotoxic-t-lymphocytes-targeting-multiple-myeloma
#19
J Bae, T Hideshima, G L Zhang, J Zhou, D B Keskin, N C Munshi, K C Anderson
X-box binding protein 1 (XBP1), CD138 (Syndecan-1) and CS1 (SLAMF7) are highly expressed antigens in cancers including multiple myeloma (MM). Here, we identify and characterize immunogenic HLA-A24 peptides derived from these antigens for potential vaccination therapy of HLA-A24+ patients with MM. The identified immunogenic HLA-A24-specific XBP1 unspliced (UN)185-193 (I S P W I L A V L), XBP1 spliced (SP)223-231 (V Y P E G P S S L), CD138265-273 (I F A V C L V G F) and CS1240-248 (L F V L G L F L W) peptides induced antigen-specific CTL with anti-MM activity in an HLA-A24 restricted manner...
March 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29051586/phosphatidylserine-induced-conformational-modulation-of-immune-cell-exhaustion-associated-receptor-tim3
#20
Jeffrey K Weber, Ruhong Zhou
In the face of chronic cancers and protracted viral infections, human immune cells are known to adopt an exhausted state in which their effector functions are lost. In recent years, a number of inhibitory receptors have been connected to the immune cell exhaustion phenotype; furthermore, ligands capable of activating these receptors have been discovered. The molecular mechanisms by which these ligands affect the exhausted states of immune cells, however, are largely unknown. Here, we present the results of molecular dynamics simulations of one potential exhaustion-associated system: the complex of human inhibitory receptor TIM3 (hTIM3) and its ligand phosphatidylserine (PSF)...
October 19, 2017: Scientific Reports
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