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tumor microenvironment

Michael B Burns, Emmanuel Montassier, Juan Abrahante, Sambhawa Priya, David E Niccum, Alexander Khoruts, Timothy K Starr, Dan Knights, Ran Blekhman
Variation in the gut microbiome has been linked to colorectal cancer (CRC), as well as to host genetic variation. However, we do not know whether, in addition to baseline host genetics, somatic mutational profiles in CRC tumors interact with the surrounding tumor microbiome, and if so, whether these changes can be used to understand microbe-host interactions with potential functional biological relevance. Here, we characterized the association between CRC microbial communities and tumor mutations using microbiome profiling and whole-exome sequencing in 44 pairs of tumors and matched normal tissues...
June 20, 2018: PLoS Genetics
Neil M Carleton, George Lee, Anant Madabhushi, Robert W Veltri
Nuclear alterations are a hallmark of many types of cancers, including prostate cancer (PCa). Recent evidence shows that subvisual changes, ones that may not be visually perceptible to a pathologist, to the nucleus and its ultrastructural components can precede visual histopathological recognition of cancer. Alterations to nuclear features, such as nuclear size and shape, texture, and spatial architecture, reflect the complex molecular-level changes that occur during oncogenesis. Quantitative nuclear morphometry, a field that uses computational approaches to identify and quantify malignancy-induced nuclear changes, can enable a detailed and objective analysis of the PCa cell nucleus...
June 20, 2018: Journal of Cellular Biochemistry
Alessandro Poggi, Serena Varesano, Maria Raffaella Zocchi
[This corrects the article on p. 262 in vol. 9, PMID: 29515580.].
2018: Frontiers in Immunology
Guoju Hong, Vincent Kuek, Jiaxi Shi, Lin Zhou, Xiaorui Han, Wei He, Jennifer Tickner, Heng Qiu, Qiushi Wei, Jiake Xu
Epidermal growth factor-like domain-containing protein 7 (EGFL7), a member of the epidermal growth factor (EGF)-like protein family, is a potent angiogenic factor expressed in many different cell types. EGFL7 plays a vital role in controlling vascular angiogenesis during embryogenesis, organogenesis, and maintaining skeletal homeostasis. It regulates cellular functions by mediating the main signaling pathways (Notch, integrin) and EGF receptor cascades. Accumulating evidence suggests that Egfl7 plays a crucial role in cancer biology by modulating tumor angiogenesis, metastasis, and invasion...
June 19, 2018: Journal of Cellular Physiology
Robert D Leone, Im-Meng Sun, Min-Hee Oh, Im-Hong Sun, Jiayu Wen, Judson Englert, Jonathan D Powell
Adenosine signaling via the A2a receptor (A2aR) is emerging as an important checkpoint of immune responses. The presence of adenosine in the inflammatory milieu or generated by the CD39/CD73 axis on tissues or T regulatory cells serves to regulate immune responses. By nature of the specialized metabolism of cancer cells, adenosine levels are increased in the tumor microenvironment and contribute to tumor immune evasion. To this end, small molecule inhibitors of the A2aR are being pursued clinically to enhance immunotherapy...
June 19, 2018: Cancer Immunology, Immunotherapy: CII
Vusala Snyder, Tamika C Reed-Newman, Levi Arnold, Sufi Mary Thomas, Shrikant Anant
Malignant tumors contain heterogeneous populations of cells in various states of proliferation and differentiation. The presence of cancer stem or initiating cells is a well-established concept wherein quiescent and poorly differentiated cells within a tumor mass contribute to drug resistance, and under permissive conditions, are responsible for tumor recurrence and metastasis. A number of studies have identified molecular markers that are characteristic of tissue-specific cancer stem cells (CSCs). Isolation of CSCs has enabled studies on the metabolic status of CSCs...
2018: Frontiers in Oncology
Ziyi Chen, Lijun Quan, Anfei Huang, Qiang Zhao, Yao Yuan, Xuye Yuan, Qin Shen, Jingzhe Shang, Yinyin Ben, F Xiao-Feng Qin, Aiping Wu
The RNA sequencing approach has been broadly used to provide gene-, pathway-, and network-centric analyses for various cell and tissue samples. However, thus far, rich cellular information carried in tissue samples has not been thoroughly characterized from RNA-Seq data. Therefore, it would expand our horizons to better understand the biological processes of the body by incorporating a cell-centric view of tissue transcriptome. Here, a computational model named seq-ImmuCC was developed to infer the relative proportions of 10 major immune cells in mouse tissues from RNA-Seq data...
2018: Frontiers in Immunology
Bassam Janji, Guy Berchem, Salem Chouaib
Cancer cells evolve in the tumor microenvironment, which is now well established as an integral part of the tumor and a determinant player in cancer cell adaptation and resistance to anti-cancer therapies. Despite the remarkable and fairly rapid progress over the past two decades regarding our understanding of the role of the tumor microenvironment in cancer development, its precise contribution to cancer resistance is still fragmented. This is mainly related to the complexity of the "tumor ecosystem" and the diversity of the stromal cell types that constitute the tumor microenvironment...
2018: Frontiers in Immunology
Muna Alemi Yahya, Shilhav Meisel Sharon, Shay Hantisteanu, Mordechai Hallak, Ilan Bruchim
Treatment of patients with gynecologic malignancies diagnosed at advanced stages remains a therapeutic challenge. Survival rates of these patients remain significantly low, despite surgery and chemotherapy. Advances in understanding the role of the immune system in the pathogenesis of cancer have led to the rapid evolution of immunotherapeutic approaches. Immunotherapeutic strategies, including targeting specific immune checkpoints, as well as dendritic cell (DC) immunotherapy are being investigated in several malignancies, including gynecological cancers...
2018: Frontiers in Endocrinology
Gorjana Rackov, Noemi Garcia-Romero, Susana Esteban-Rubio, Josefa Carrión-Navarro, Cristobal Belda-Iniesta, Angel Ayuso-Sacido
Extracellular vesicles (EVs) - including exosomes, microvesicles and apoptotic bodies - have received much scientific attention last decade as mediators of a newly discovered cell-to-cell communication system, acting at short and long distances. EVs carry biologically active molecules, thus providing signals that influence a spectrum of functions in recipient cells during various physiological and pathological processes. Recent findings point to EVs as very attractive immunomodulatory therapeutic agents, vehicles for drug delivery and diagnostic and prognostic biomarkers in liquid biopsies...
2018: Frontiers in Physiology
Chiraz Atri, Fatma Z Guerfali, Dhafer Laouini
Experimental models have often been at the origin of immunological paradigms such as the M1/M2 dichotomy following macrophage polarization. However, this clear dichotomy in animal models is not as obvious in humans, and the separating line between M1-like and M2-like macrophages is rather represented by a continuum, where boundaries are still unclear. Indeed, human infectious diseases, are characterized by either a back and forth or often a mixed profile between the pro-inflammatory microenvironment (dominated by interleukin (IL)-1β, IL-6, IL-12, IL-23 and Tumor Necrosis Factor (TNF)-α cytokines) and tissue injury driven by classically activated macrophages (M1-like) and wound healing driven by alternatively activated macrophages (M2-like) in an anti-inflammatory environment (dominated by IL-10, Transforming growth factor (TGF)-β, chemokine ligand (CCL)1, CCL2, CCL17, CCL18, and CCL22)...
June 19, 2018: International Journal of Molecular Sciences
Takuya Kato, Kazuhiro Noma, Toshiaki Ohara, Hajime Kashima, Yuki Katsura, Hiroaki Sato, Satoshi Komoto, Ryoichi Katsube, Takayuki Ninomiya, Hiroshi Tazawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara
PURPOSE: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a central role in tumor progression. We investigated whether CAFs can regulate tumor-infiltrating lymphocytes (TILs) and their role in tumor immunosuppression. EXPERIMENTAL DESIGN: 140 cases of esophageal cancer were analyzed for CAFs and CD8+ or forkhead box protein 3 (FoxP3+ ) TILs by immunohistochemistry. We analyzed cytokines using murine or human fibroblasts and cancer cells...
June 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Suvi Luoto, Ismaïl Hermelo, Elisa M Vuorinen, Paavo Hannus, Juha Kesseli, Matti Nykter, Kirsi J Granberg
The immunosuppressive microenvironment in glioblastoma (GBM) prevents an efficient antitumoral immune response and enables tumor formation and growth. Although an understanding of the nature of immunosuppression is still largely lacking, it is important for successful cancer treatment through immune system modulation. To gain insight into immunosuppression in GBM, we performed a computational analysis to model relative immune cell content and type of immune response in each GBM tumor sample from The Cancer Genome Atlas RNA-seq dataset...
June 19, 2018: Cancer Research
Tayaba Ismail, Hyun-Kyung Lee, Chowon Kim, Taejoon Kwon, Tae Joo Park, Hyun-Shik Lee
The lysine-specific histone demethylase 1A (KDM1A) was the first demethylase to challenge the concept of the irreversible nature of methylation marks. KDM1A, containing a flavin adenine dinucleotide (FAD)-dependent amine oxidase domain, demethylates histone 3 lysine 4 and histone 3 lysine 9 (H3K4me1/2 and H3K9me1/2). It has emerged as an epigenetic developmental regulator and was shown to be involved in carcinogenesis. The functional diversity of KDM1A originates from its complex structure and interactions with transcription factors, promoters, enhancers, oncoproteins, and tumor-associated genes (tumor suppressors and activators)...
June 19, 2018: Epigenetics & Chromatin
Justin Zonneville, Alfiya Safina, Alexander M Truskinovsky, Carlos L Arteaga, Andrei V Bakin
BACKGROUND: The breast cancer microenvironment promotes tumor vascularization through the complex interactions involving tumor-associated fibroblasts (TAFs). Emerging data indicate that TAFs increase production and signaling by TGF-β cytokines, while the role of TGF-β signaling in the regulation of tumor blood vessels is not fully understood. The current study presents evidence that TAFs enhance the organization of tumor blood capillaries, and TGF-β signaling plays an important role in this response...
June 19, 2018: BMC Cancer
Di Lu, Yang An, Simin Feng, Xiaodan Li, Aiping Fan, Zheng Wang, Yanjun Zhao
The complex design of multifunctional nanomedicine is beneficial to overcome the multiple biological barriers of drug delivery, but it also presents additional hurdles to clinical translation (e.g., scaling-up and quality control). To address this dilemma, we employed a simple imidazole-bearing polymer micelle for enhanced cellular uptake, facilitated endosomal escape, and on-demand release of a model drug, SN-38. The micelles were crosslinked by the reversible imidazole/Zn2+ coordination with a drug loading of ca...
June 18, 2018: AAPS PharmSciTech
Zhe Sun, Zeng Yi, Xinxing Cui, Xiangyu Chen, Wen Su, Xiaoxiang Ren, Xudong Li
The development of safe and effective nano-drug delivery systems to deliver anticancer drugs to targeted cells and organs is crucial to enhance the therapeutic efficacy and overcome unwanted side effects of chemotherapy. Herein, we prepared CD44-targeted dual-stimuli responsive human hair keratin and hyaluronic acid nanogels (KHA-NGs) through a simple crosslinking method. KHA-NGs, which consisted of spheres 50 nm in diameter, were used as carriers to load the anticancer drug doxorubicin hydrochloride (DOX)...
June 19, 2018: Nanoscale
Kazuyasu Fujii
Primary cutaneous lymphomas comprise a group of lymphatic malignancies that occur primarily in the skin. They represent the second most common form of extranodal non-Hodgkin's lymphoma and are characterized by heterogeneous clinical, histological, immunological, and molecular features. The most common type is mycosis fungoides and its leukemic variant, Sézary syndrome. Both diseases are considered T-helper cell type 2 (Th2) diseases. Not only the tumor cells but also the tumor microenvironment can promote Th2 differentiation, which is beneficial for the tumor cells because a Th1 environment enhances antitumor immune responses...
2018: Frontiers in Oncology
Christoph Renner, Frank Stenner
Patients with classical Hodgkin lymphoma (cHL) have an impaired cellular immune response as indicated by an anergic reaction against standard recall antigens and a diminished rejection reaction of allogeneic skin transplant. This clinical observation can be linked to the histopathological feature of cHL since the typical pattern of a cHL manifestation is characterized by sparse large CD30+ tumor-infiltrating Hodgkin-Reed-Sternberg (HRS) cells that are surrounded by a dense inflammatory immune microenvironment with mixed cellularity...
2018: Frontiers in Oncology
Yangyang Liu, Yadi Cai, Li Liu, Yudong Wu, Xiangyang Xiong
Chemokine (C-C motif) ligand 7 (CCL7), a CC chemokine, is a chemotactic factor and attractant for various kinds of leukocytes, including monocytes and neutrophils. CCL7 is widely expressed in multiple cell types and can participate in anti-inflammatory responses through binding to its receptors to mediate the recruitment of immune cells. Abnormal CCL7 expression is associated with certain immune diseases. Furthermore, CCL7 plays a pivotal role in tumorigenesis. CCL7 promotes tumor progression by supporting the formation of the tumor microenvironment and facilitating tumor invasion and metastasis, although some studies have suggested that CCL7 has tumor suppressor effects...
2018: PeerJ
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