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https://www.readbyqxmd.com/read/27913998/immunotherapy-for-breast-cancer-past-present-and-future
#1
Alison Spellman, Shou-Ching Tang
Immunotherapy has shown promise in many solid tumors including melanoma and non-small cell lung cancer with an evolving role in breast cancer. Immunotherapy encompasses a wide range of therapies including immune checkpoint inhibition, monoclonal antibodies, bispecific antibodies, vaccinations, antibody-drug conjugates, and identifying other emerging interventions targeting the tumor microenvironment. Increasing efficacy of these treatments in breast cancer patients requires identification of better biomarkers to guide patient selection; recognizing when to initiate these therapies in multi-modality treatment plans; establishing novel assays to monitor immune-mediated responses; and creating combined systemic therapy options incorporating conventional treatments such as chemotherapy and endocrine therapy...
December 2, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27913523/advances-and-practical-use-of-monoclonal-antibodies-in-multiple-myeloma-therapy
#2
Hans C Lee, Donna M Weber
The use of proteasome inhibitors and immunomodulatory agents in the treatment of myeloma have resulted in significant improvements in patient outcomes over the last decade. Although these agents now form the backbone of current myeloma treatment regimens both in the frontline and in a relapsed setting, drug resistance remains an inevitable challenge that most patients will encounter during their disease course. Hence, new treatment strategies continue to be explored, and the recent regulatory approvals of the monoclonal antibodies (mAbs) daratumumab (DARA) and elotuzumab (ELO), which target the plasma cell surface proteins CD38 and signaling lymphocytic activation molecule F7 (SLAMF7), respectively, have heralded the long-awaited era of antibody-based approaches in the treatment of myeloma...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913493/novel-agents-in-follicular-lymphoma-choosing-the-best-target
#3
Laurie H Sehn
Outcomes in patients with follicular lymphoma (FL) have improved dramatically over the last decade. However, novel agents are greatly needed for those who exhibit treatment resistance, in order to minimize lifelong toxicity and to enable combinations that may allow us to achieve the elusive goal of cure. Biological advances have led to the discovery of a large number of potential therapeutic targets and the development of a plethora of novel agents designed to exploit these processes. Possible targets include tumor cell surface markers, key components of intracellular pathways and epigenetic mechanisms, and reactive cells of the microenvironment...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913437/surface-expression-of-tgf%C3%AE-docking-receptor-garp-promotes-oncogenesis-and-immune-tolerance-in-breast-cancer
#4
Alessandra Metelli, Bill X Wu, Caroline W Fugle, Saleh Rachidi, Shaoli Sun, Yongliang Zhang, Jennifer Wu, Stephen Tomlinson, Philip H Howe, Yi Yang, Elizabeth Garrett-Mayer, Bei Liu, Zihai Li
GARP encoded by the Lrrc32 gene is the cell surface docking receptor for latent TGFβ, which is expressed naturally by platelets and regulatory T cells (Treg). Although Lrrc32 is amplified frequently in breast cancer, the expression and relevant functions of GARP in cancer have not been explored. Here, we report that GARP exerts oncogenic effects, promoting immune tolerance by enriching and activating latent TGFβ in the tumor microenvironment. We found that human breast, lung, and colon cancers expressed GARP aberrantly...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27912844/heparanase-from-basic-research-to-therapeutic-applications-in-cancer-and-inflammation
#5
Israel Vlodavsky, Preeti Singh, Ilanit Boyango, Lilach Gutter-Kapon, Michael Elkin, Ralph D Sanderson, Neta Ilan
Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Numerous clinical association studies have consistently demonstrated that upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. In contrast, knockdown of heparanase or treatments of tumor-bearing mice with heparanase-inhibiting compounds, markedly attenuate tumor progression further underscoring the potential of anti-heparanase therapy for multiple types of cancer...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27912781/an-immune-stratification-reveals-a-subset-of-pd-1-lag-3-double-positive-triple-negative-breast-cancers
#6
Giulia Bottai, Carlotta Raschioni, Agnese Losurdo, Luca Di Tommaso, Corrado Tinterri, Rosalba Torrisi, Jorge S Reis-Filho, Massimo Roncalli, Christos Sotiriou, Armando Santoro, Alberto Mantovani, Sherene Loi, Libero Santarpia
BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC. METHODS: Formalin-fixed, paraffin-embedded tissues were retrospectively collected from a cohort of patients with early-stage TNBC treated with adjuvant anthracycline-based chemotherapy (n = 259)...
December 3, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27912145/chloroquine-cq-exerts-anti-breast-cancer-through-modulating-microenvironment-and-inducing-apoptosis
#7
Yanjun Zhang, Yu Cao, Xiaodan Sun, Yonghui Feng, Yunting Du, Fei Liu, Chunyun Yu, Feng Jin
CQ is an anti-malaria drug, which has been used for years. However, there are published articles about its activity in anti-cancers. The aim of this approach was to look at possibility and related mechanisms of anti-breast cancer (mouse breast cancer cell line 4T1) by CQ alone. The studies of anti 4T1 in vitro and in vivo by CQ were performed. The growth of 4T1 in vitro and in vivo, survival of mice post treatment with CQ, changes of immune parameters and microenvironment in mice were evaluated. Our results demonstrate that CQ could markedly inhibit growth of 4T1 in vitro through inducing apoptosis of cells, inhibiting secretion of TGF-β and prolong the mice survival in vivo through boosting immune system by upregulating CD8+ T cell, and through down-regulating tumor associated macrophages (TAM), myeloid derived suppressing cells (MDSC) and Tregs, in microenvironment of mice bearing tumor...
November 29, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#8
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27910857/myeloid-derived-suppressor-cells-and-their-role-in-pancreatic-cancer
#9
REVIEW
M Pergamo, G Miller
Pancreatic cancer is a devastating disease and ranks as the third most common cause of cancer-related death. Like many cancers, there has been increased interest in the role of the immune system in the progression and development of pancreatic cancer. In particular, immunosuppression within the tumor microenvironment (TME) is thought to impair the host's antitumor response. In this article, we review myeloid-derived suppressor cells and their contribution to this immunosuppression within the pancreatic TME...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27908931/filling-the-tank-keeping-antitumor-t-cells-metabolically-fit-for-the-long-haul
#10
REVIEW
Greg M Delgoffe
Discoveries in tumor immunology and subsequent clinical advances in cancer immunotherapy have revealed that the immune system is not oblivious to tumor progression but heavily interacts with developing neoplasia and malignancy. A major factor preventing immune destruction is the establishment of a highly immunosuppressive tumor microenvironment (TME), which provides architecture to the tumor, supports indirect means of immunosuppression such as the recruitment of tolerogenic cells like regulatory T cells and myeloid-derived suppressor cells (MDSC), and represents a zone of metabolically dearth conditions...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27907202/a-reproducible-method-for-isolation-and-in-vitro-culture-of-functional-human-lymphoid-stromal-cells-from-tonsils
#11
Yotam E Bar-Ephraim, Tanja Konijn, Mehmet Gönültas, Reina E Mebius, Rogier M Reijmers
The stromal compartment of secondary lymphoid organs is classicaly known for providing a mechanical scaffold for the complex interactions between hematopoietic cells during immune activation as well as for providing a niche which is favorable for survival of lymphocytes. In recent years, it became increasingly clear that these cells also play an active role during such a response. Currently, knowledge of the interactions between human lymphoid stroma and hematopoietic cells is still lacking and most insight is based on murine systems...
2016: PloS One
https://www.readbyqxmd.com/read/27906187/systemic-application-of-3-methyladenine-markedly-inhibited-atherosclerotic-lesion-in-apoe-mice-by-modulating-autophagy-foam-cell-formation-and-immune-negative-molecules
#12
Shen Dai, Bo Wang, Wen Li, Liyang Wang, Xingguo Song, Chun Guo, Yulan Li, Fengming Liu, Faliang Zhu, Qun Wang, Xiaoyan Wang, Yongyu Shi, Jianing Wang, Wei Zhao, Lining Zhang
A growing body of evidence demonstrates that autophagy, an evolutionarily conserved intracellular degradation process, is involved in the pathogenesis of atherosclerosis and has become a potential therapeutic target. Here we tested the effect of two inhibitors of phosphatidylinositol 3-kinase, 3-methyladenine (3-MA) and 2-(4-morpholinyl)-8-phenyl-chromone (LY294002), commonly used as inhibitors of autophagy, in atherosclerosis in apolipoprotein E(-/-) mice. Systemic application of 3-MA but not LY294002 markedly reduced the size of atherosclerotic plaque and increased the stability of lesions in high-fat diet-fed mice as compared with controls...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906184/1-methyl-tryptophan-attenuates-regulatory-t-cells-differentiation-due-to-the-inhibition-of-estrogen-ido1-mrc2-axis-in-endometriosis
#13
Chunyan Wei, Jie Mei, Lingli Tang, Yukai Liu, Dajin Li, Mingqing Li, Xiaoyong Zhu
Foxp3(+) regulatory T (Treg) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal Treg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal Treg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906162/activation-of-myeloid-and-endothelial-cells-by-cd40l-gene-therapy-supports-t-cell-expansion-and-migration-into-the-tumor-microenvironment
#14
E Eriksson, R Moreno, I Milenova, L Liljenfeldt, L C Dieterich, L Christiansson, H Karlsson, G Ullenhag, S Mangsbo, A Dimberg, R Alemany, A Loskog
CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate Th1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer...
December 1, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27905556/cellular-aspartyl-proteases-promote-the-unconventional-secretion-of-biologically-active-hiv-1-matrix-protein-p17
#15
Francesca Caccuri, Maria Luisa Iaria, Federica Campilongo, Kristen Varney, Alessandro Rossi, Stefania Mitola, Silvia Schiarea, Antonella Bugatti, Pietro Mazzuca, Cinzia Giagulli, Simona Fiorentini, Wuyuan Lu, Mario Salmona, Arnaldo Caruso
The human immune deficiency virus type 1 (HIV-1) matrix protein p17 (p17), although devoid of a signal sequence, is released by infected cells and detected in blood and in different organs and tissues even in HIV-1-infected patients undergoing successful combined antiretroviral therapy (cART). Extracellularly, p17 deregulates the function of different cells involved in AIDS pathogenesis. The mechanism of p17 secretion, particularly during HIV-1 latency, still remains to be elucidated. A recent study showed that HIV-1-infected cells can produce Gag without spreading infection in a model of viral latency...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905000/decidual-natural-killer-cells-and-the-immune-microenvironment-at-the-maternal-fetal-interface
#16
REVIEW
Binqing Fu, Haiming Wei
During early pregnancy, an orchestrated evolutionary maternal adaption toward tolerance of the semiallogeneic fetus is required to ensure decidualization and early embryo development. Remodeling of the immune system involves natural killer cells (NKs), macrophages, T cells and dendritic cells (DCs) altering the microenvironment in the deciduas. In particular, a unique population of NK cells with a CD56(bright)CD16(-) phenotype in the decidua has been proposed to play a key role in the maternal adaptation to pregnancy...
November 29, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27904768/combined-vegfr-and-ctla-4-blockade-increases-the-antigen-presenting-function-of-intratumoral-dcs-and-reduces-the-suppressive-capacity-of-intratumoral-mdscs
#17
Stephanie Du Four, Sarah K Maenhout, Simone P Niclou, Kris Thielemans, Bart Neyns, Joeri L Aerts
Melanoma brain metastases (MBM) occur in 10% to 50% of melanoma patients. They are often associated with a high morbidity and despite the improvements in the treatment of advanced melanoma, including immunotherapy, patients with MBM still have a poor prognosis. Antiangiogenic treatment was shown to reduce the immunosuppressive tumor microenvironment. Therefore we investigated the effect of the combination of VEGFR- and CTLA-4 blockade on the immune cells within the tumor microenvironment. In this study we investigated the effect of the combination of axitinib, a TKI against VEGFR-1, -2 and -3, with therapeutic inhibition of CTLA-4 in subcutaneous and intracranial mouse melanoma models...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27904752/the-role-of-immune-checkpoint-inhibition-in-the-treatment-of-ovarian-cancer
#18
REVIEW
Stéphanie L Gaillard, Angeles A Secord, Bradley Monk
The introduction of immune checkpoint inhibitors has revolutionized treatment of multiple cancers and has bolstered interest in this treatment approach. So far, emerging clinical data show limited clinical efficacy of these agents in ovarian cancer with objective response rates of 10-15% with some durable responses. In this review, we present emerging clinical data of completed trials of immune checkpoint inhibitors and review ongoing studies. In addition we examine the current knowledge of the tumor microenvironment of ovarian cancers with a focus on the significance of PD-L1 expression and tumor-infiltrating lymphocytes on predicting response to immune checkpoint blockade...
2016: Gynecologic Oncology Research and Practice
https://www.readbyqxmd.com/read/27904527/effect-of-th1-th2-cytokine-administration-on-proinflammatory-skov-3-cell-activation
#19
Aleksandra Mielczarek-Palacz, Justyna Sikora, Zdzisława Kondera-Anasz, Patrycja Mickiewicz, Adam Mickiewicz
INTRODUCTION: Interleukin(IL)-1β, IL-6 and IL-12 might associate with inflammatory processes in a tumor progression and create a specific microenvironment for tumor growth. The aim of the study was to assess whether the Th1 and Th2 type cytokines, such as IL-2 and IL-10, affect ovarian carcinoma continuous cell line (SKOV-3) pro-inflammatory activation. MATERIAL AND METHODS: SKOV-3 ovarian cells and peripheral blood mononuclear cells (PBMCs) were stimulated by IL-2 and IL-10...
December 1, 2016: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/27903982/m2-like-tumor-associated-macrophages-drive-vasculogenic-mimicry-through-amplification-of-il-6-expression-in-glioma-cells
#20
Lin Zhang, Yangyang Xu, Jintang Sun, Weiliang Chen, Lei Zhao, Chao Ma, Qingjie Wang, Jia Sun, Bin Huang, Yun Zhang, Xingang Li, Xun Qu
Vasculogenic mimicry (VM) has offered a new horizon for understanding tumor angiogenesis, but the mechanisms of VM in glioma progression have not been studied explicitly until now. As a significant component of immune infiltration in tumor microenvironment, macrophages have been demonstrated to play an important role in tumor growth and angiogenesis. However, whether macrophages could play a potential key role in glioma VM is still poorly understood. Herein we reported that both VM and CD163+ cells were associated with WHO grade and reduced patient survival, and VM channel counting was correlated to the number of infiltrated CD163+ cells in glioma specimens...
November 26, 2016: Oncotarget
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