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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/29757670/regulatory-t-cell-dynamics-with-abatacept-treatment-in-rheumatoid-arthritis
#2
Kane Langdon, Nagaraja Haleagrahara
The progressive damage in rheumatoid arthritis (RA) has been linked to an increase in inflammatory Th1/Th17 cells and a decrease in number or function of immunomodulatory regulatory T cells (Tregs). Many therapies that are effective in RA are shown to affect Th1/Th17 cells and/or Tregs. One such therapy, abatacept, utilizes a physiologic immunomodulatory molecule called cytotoxic lymphocyte antigen-4 (CTLA-4) which causes contact-dependent inhibition of inflammatory T-cell activation. Recent advances in CTLA-4 research has uncovered the method by which this occurs physiologically but the actions of the CTLA-4Ig fusion protein are still not fully understood...
May 14, 2018: International Reviews of Immunology
https://www.readbyqxmd.com/read/29728568/egr2-independent-klf1-mediated-induction-of-pd-l1-in-cd4-t-cells
#3
Shuzo Teruya, Tomohisa Okamura, Toshihiko Komai, Mariko Inoue, Yukiko Iwasaki, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto, Keishi Fujio
Programmed death ligand 1 (PD-L1)-mediated induction of immune tolerance has been vigorously investigated in autoimmunity and anti-tumor immunity. However, details of the mechanism by which PD-L1 is induced in CD4+ T cells are unknown. Here, we revealed the potential function of Klf1 and Egr2-mediated induction of PD-L1 in CD4+ T cells. We focused on the molecules specifically expressed in CD4+ CD25- LAG3+ regulatory T cells (LAG3+ Tregs) highly express of PD-L1 and transcription factor Egr2. Although ectopic expression of Egr2 induced PD-L1, a deficiency of Egr2 did not affect its expression, indicating the involvement of another PD-L1 induction mechanism...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29716923/interferon-gamma-messenger-rna-signature-in-tumor-biopsies-predicts-outcomes-in-patients-with-non-small-cell-lung-carcinoma-or-urothelial-cancer-treated-with-durvalumab
#4
Brandon W Higgs, Christopher Morehouse, Katie L Streicher, Philip Brohawn, Fernanda Pilataxi, Ashok Gupta, Koustubh Ranade
PURPOSE: To identify a predictive biomarker for durvalumab, an anti-programmed death ligand 1 (PD-L1) monoclonal antibody. EXPERIMENTAL DESIGN: RNA sequencing of 97 advanced-stage non-small-cell lung carcinoma (NSCLC) biopsies from a nonrandomized phase 1b/2 clinical trial (1108/NCT01693562) were profiled to identify a predictive signature; 62 locally advanced or metastatic urothelial cancer (UC) tumors from the same study were profiled to confirm predictive utility of the signature...
May 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29714078/overexpression-of-p21-activated-kinase-2-is-correlated-with-high-grade-oral-squamous-cell-carcinomas
#5
Yao Xiao, Wei-Wei Deng, Lei-Lei Yang, Hao Li, Guang-Tao Yu, Wen-Feng Zhang, Zhi-Jun Sun
AIM: p21-activated kinase 2 (PAK2) is overexpressed in several tumors but the expression of PAK2 in oral squamous cell carcinomas (OSCCs) remains unclear. MATERIALS & METHODS: Immunohistochemistry was performed on human tissue microarrays containing 165 primary OSCC, 48 oral epithelial dysplasia and 43 normal oral mucosa. RESULTS: PAK2 expression was increased in primary OSCC compared with normal mucosa and significantly increased in primary OSCC grade III compared with grade I, but independent of overall survival rate...
May 1, 2018: Future Oncology
https://www.readbyqxmd.com/read/29710228/immune-profiling-of-premalignant-lesions-in-patients-with-lynch-syndrome
#6
Kyle Chang, Melissa W Taggart, Laura Reyes-Uribe, Ester Borras, Erick Riquelme, Reagan M Barnett, Guido Leoni, F Anthony San Lucas, Maria T Catanese, Federica Mori, Maria G Diodoro, Y Nancy You, Ernest T Hawk, Jason Roszik, Paul Scheet, Scott Kopetz, Alfredo Nicosia, Elisa Scarselli, Patrick M Lynch, Florencia McAllister, Eduardo Vilar
Importance: Colorectal carcinomas in patients with Lynch syndrome (LS) arise in a background of mismatch repair (MMR) deficiency, display a unique immune profile with upregulation of immune checkpoints, and response to immunotherapy. However, there is still a gap in understanding the pathogenesis of MMR-deficient colorectal premalignant lesions, which is essential for the development of novel preventive strategies for LS. Objective: To characterize the immune profile of premalignant lesions from a cohort of patients with LS...
April 16, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29599411/cd103-tumor-resident-cd8-t-cells-are-associated-with-improved-survival-in-immunotherapy-na%C3%A3-ve-melanoma-patients-and-expand-significantly-during-anti-pd-1-treatment
#7
Jarem Edwards, James S Wilmott, Jason Madore, Tuba Nur Gide, Camelia Quek, Annie Tasker, Angela Ferguson, Jinbiao Chen, Rehana Hewavisenti, Peter Hersey, Thomas Gebhardt, Wolfgang Weninger, Warwick J Britton, Robyn P M Saw, John F Thompson, Alexander M Menzies, Georgina V Long, Richard A Scolyer, Umaimainthan Palendira
Purpose: Therapeutic blockade of immune checkpoints has revolutionized cancer treatment. Durable responses, however, occur in less than half of those treated, and efforts to improve treatment efficacy are confounded by a lack of understanding of the characteristics of the cells that initiate antitumor immune response. Experimental Design: We performed multiparameter flow cytometry and quantitative multiplex immunofluorescence staining on tumor specimens from immunotherapy-naïve melanoma patients and longitudinal biopsy specimen obtained from patients undergoing anti-PD-1 therapy...
March 29, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
#8
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/29535721/early-growth-response-gene-2-expressing-cd4-lag3-regulatory-t-cells-the-therapeutic-potential-for-treating-autoimmune-diseases
#9
REVIEW
Tomohisa Okamura, Kazuhiko Yamamoto, Keishi Fujio
Regulatory T cells (Tregs) are necessary for the maintenance of immune tolerance. Tregs are divided into two major populations: one is thymus derived and the other develops in the periphery. Among these Tregs, CD4+ CD25+ Tregs, which mainly originate in the thymus, have been extensively studied. Transcription factor Foxp3 is well known as a master regulatory gene for the development and function of CD4+ CD25+ Tregs. On the other hand, peripheral Tregs consist of distinct cell subsets including Foxp3-dependent extrathymically developed Tregs and interleukin (IL)-10-producing type I regulatory T (Tr1) cells...
2018: Frontiers in 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
#10
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/29520442/cd274-lag3-and-ido1-expressions-in-tumor-infiltrating-immune-cells-as-prognostic-biomarker-for-patients-with-msi-high-colon-cancer
#11
Soo Jung Lee, Sun-Young Jun, In Hee Lee, Byung Woog Kang, Su Yeon Park, Hye Jin Kim, Jun Seok Park, Gyu-Seog Choi, Ghilsuk Yoon, Jong Gwang Kim
PURPOSE: This study attempted to reveal the prognostic impact of microsatellite instability-high (MSI-H) colon cancer with tumor-infiltrating immune cells (TIICs) and immune checkpoint protein expression, which are good candidates for immunotherapy. MATERIALS AND METHODS: The study included 89 patients with MSI-H colon cancer who underwent curative surgery at Kyungpook National University Chilgok Hospital. The expression status of specific inhibitory receptors, such as CD274 (programmed death-ligand 1, PD-L1), PDCD1 (programmed cell death 1, PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte-activation gene 3 (LAG3), and indolamine 2'3'-dioxygenase 1 (IDO1), was retrospectively analyzed using immunohistochemistry (IHC)...
June 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29510256/transcriptome-profiling-analysis-of-grouper-during-nervous-necrosis-virus-persistent-infection
#12
Chun-Hsi Tso, Ming-Wei Lu
Nervous necrosis virus (NNV) infection has been considered a serious disease in farmed grouper. Particularly, the persistent infection model conducts the grouper into a carrier state that continues to spread the virus through spawning. This particular model makes disease control more difficult in the aquaculture industry. In the present study, we used RNA-Seq, a high-throughput method based on next-generation sequencing, to profile the expression of genes during the period of NNV persistent infection. We evaluated the transcriptomic changes in the brain tissue of grouper...
May 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29484121/novel-mutational-landscapes-and-expression-signatures-of-lung-squamous-cell-carcinoma
#13
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
#14
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/29439955/dual-pd1-lag3-immune-checkpoint-blockade-limits-tumor-development-in-a-murine-model-of-chronic-lymphocytic-leukemia
#15
LETTER
Marina Wierz, Sandrine Pierson, Léa Guyonnet, Elodie Viry, Audrey Lequeux, Anaïs Oudin, Simone P Niclou, Markus Ollert, Guy Berchem, Bassam Janji, Coralie Guérin, Jerome Paggetti, Etienne Moussay
No abstract text is available yet for this article.
April 5, 2018: Blood
https://www.readbyqxmd.com/read/29427592/establishment-of-engineered-cell-based-assays-mediating-lag3-and-pd1-immune-suppression-enables-potency-measurement-of-blocking-antibodies-and-assessment-of-signal-transduction
#16
Bhagyashree Bhagwat, Holly Cherwinski, Manjiri Sathe, Wolfgang Seghezzi, Terrill K McClanahan, Rene de Waal Malefyt, Aarron Willingham
LAG3 is an important regulator of T cell homeostasis and studies in mouse tumor models have demonstrated that simultaneously antagonizing LAG3 and PD1 can augment tumor-specific T cell responses and induce tumor rejection. The combined use of LAG3 antagonist antibodies with established anti-PD1 therapies is currently being evaluated in human clinical trials. A functional assay for human LAG3 was developed by co-culture of a Jurkat T-cell lymphoma line overexpressing LAG3 with a Raji B-cell lymphoma line in the presence of staphylococcal enterotoxins...
May 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29415983/14-3-3%C3%AE-delivered-by-hepatocellular-carcinoma-derived-exosomes-impaired-anti-tumor-function-of-tumor-infiltrating-t-lymphocytes
#17
Xiaochen Wang, Haiyuan Shen, Guangyan Zhangyuan, Ruyi Huang, Wenjie Zhang, Qifeng He, Kangpeng Jin, Han Zhuo, Zechuan Zhang, Jincheng Wang, Beicheng Sun, Xiaojie Lu
Increasing evidence shows that the anti-tumor functions of tumor-infiltrating T lymphocytes (TILs) were inhibited significantly, but the underlying mechanisms remain not fully understood. In this study, we found that 14-3-3ζ expression was up-regulated in hepatocellular carcinoma (HCC) cells and in TILs. TILs with 14-3-3ζ high-expression (14-3-3ζhigh ) exhibited impaired activation (CD69), proliferation (Ki67) and anti-tumor functions compared to 14-3-3ζ low expression (14-3-3ζlow ) TILs. Flow cytometry assay showed that compared with 14-3-3ζlow CD8+ T cells, 14-3-3ζhigh ones exhibited higher frequency of exhausted phenotypes as measured by inhibitory receptors such as PD-1, TIM-3, LAG3, and CTLA-4...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29408194/association-between-air-pollution-and-upper-respiratory-tract-infection-in-hospital-outpatients-aged-0-14-years-in-hefei-china-a-time-series-study
#18
Y R Li, C C Xiao, J Li, J Tang, X Y Geng, L J Cui, J X Zhai
OBJECTIVE: To investigate the association between air pollution and upper respiratory tract infection (URTI) in children aged 0-14 years in Hefei, China in 2014-2015. STUDY DESIGN: An ecological method (i.e. generalised additive model [GAM]) was used to explore the effects of air pollutants on paediatric hospital outpatients with URTI. METHODS: GAM was used to evaluate the lag effects (including lag0 to lag6, lag01 and lag06) between daily changes in particulate matter (PM10 ), fine particulate matter (PM2...
March 2018: Public Health
https://www.readbyqxmd.com/read/29399401/a-safe-and-highly-efficient-tumor-targeted-type-i-interferon-immunotherapy-depends-on-the-tumor-microenvironment
#19
Anje Cauwels, Sandra Van Lint, Geneviève Garcin, Jennyfer Bultinck, Franciane Paul, Sarah Gerlo, José Van der Heyden, Yann Bordat, Dominiek Catteeuw, Lode De Cauwer, Elke Rogge, Annick Verhee, Gilles Uzé, Jan Tavernier
Despite approval for the treatment of various malignancies, clinical application of cytokines such as type I interferon (IFN) is severely impeded by their systemic toxicity. AcTakines (Activity-on-Target cytokines) are optimized immunocytokines that, when injected in mice, only reveal their activity upon cell-specific impact. We here show that type I IFN-derived AcTaferon targeted to the tumor displays strong antitumor activity without any associated toxicity, in contrast with wild type IFN. Treatment with CD20-targeted AcTaferon of CD20+ lymphoma tumors or melanoma tumors engineered to be CD20+ , drastically reduced tumor growth...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29383101/cxcr2-mdscs-promote-breast-cancer-progression-by-inducing-emt-and-activated-t-cell-exhaustion
#20
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
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