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tumor immunological microenvironment

Denise Lau, Alexandria M Bobe, Aly A Khan
RNA sequencing (RNA-seq) provides an efficient high-throughput technique to robustly characterize the tumor immune microenvironment (TME). The increasing use of RNA-seq in clinical and basic science settings provides a powerful opportunity to access novel therapeutic biomarkers in the TME. Advanced computational methods are making it possible to resolve the composition of the tumor immune infiltrate, infer the immunological phenotypes of those cells, and assess the immune receptor repertoire in RNA-seq data...
March 2019: Trends in Cancer
Marcus A Alvarez, Júlia Pedó Freitas, S Mazher Hussain, Evan S Glazer
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancerrelated mortality in the USA, and the overall incidence of the disease is increasing such that it is expected to be the third leading cause of cancer-related deaths in the next decade. Minimal improvements in therapy have not changed the overall mortality rate over the past decade for patients with PDAC. The purpose of this review is to identify new data regardign the role of Transforming growth factor beta (TGF-β) based therapeuics in patients with PDAC...
March 20, 2019: Journal of Gastrointestinal Cancer
Jan Philipp Bewersdorf, Maximilian Stahl, Amer M Zeidan
Immune system evasion is essential for tumor cell survival and is mediated by the immunosuppressive tumor microenvironment and the activation of inhibitory immune checkpoints. While immune checkpoint-based therapy yielded impressive results in several advanced solid malignancies such as melanoma and non-small cell lung cancer, its role in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is still evolving. Areas covered: Here we review the immunology in the tumor microenvironment in the bone marrow and discuss the current preclinical and clinical data for immune checkpoint-based therapy in myeloid neoplasms...
March 19, 2019: Expert Review of Anticancer Therapy
Mateusz Rytelewski, Karine Haryutyunan, Felix Nwajei, Meenakshi Shanmugasundaram, Patrick Wspanialy, M Anna Zal, Chao-Hsien Chen, Mirna El Khatib, Shane Plunkett, Sergei A Vinogradov, Marina Konopleva, Tomasz Zal
BACKGROUND: Low availability of oxygen in tumors contributes to the hostility of the tumor microenvironment toward the immune system. However, the dynamic relationship between local oxygen levels and the immune surveillance of tumors by tumor infiltrating T-lymphocytes (TIL) remains unclear. This situation reflects a methodological difficulty in visualizing oxygen gradients in living tissue in a manner that is suitable for spatiotemporal quantification and contextual correlation with individual cell dynamics tracked by typical fluorescence reporter systems...
March 18, 2019: Journal for Immunotherapy of Cancer
Mathieu J F Crupi, John C Bell, Ragunath Singaravelu
Cancer stem cells (CSCs) have the capacity to self-renew and differentiate to give rise to heterogenous cancer cell lineages in solid tumors. These CSC populations are associated with metastasis, tumor relapse and resistance to conventional anti-cancer therapies. Here, we focus on the use of oncolytic viruses (OVs) to target CSCs as well as the OV-driven interferon production in the tumor microenvironment (TME) that can repress CSC properties. We explore the ability of OVs to deliver combinations of immune-modulating therapeutic transgenes, such as immune checkpoint inhibitor antibodies...
March 15, 2019: Stem Cells
Laura Follia, Giulio Ferrero, Giorgia Mandili, Marco Beccuti, Daniele Giordano, Rosella Spadi, Maria Antonietta Satolli, Andrea Evangelista, Hiroyuki Katayama, Wang Hong, Amin A Momin, Michela Capello, Samir M Hanash, Francesco Novelli, Francesca Cordero
Background: Most of the patients with Pancreatic Ductal Adenocarcinoma (PDA) are not eligible for a curative surgical resection. For this reason there is an urgent need for personalized therapies. PDA is the result of complex interactions between tumor molecular profile and metabolites produced by its microenvironment. Despite recent studies identified PDA molecular subtypes, its metabolic classification is still lacking. Methods: We applied an integrative analysis on transcriptomic and genomic data of glycolytic genes in PDA...
2019: Frontiers in Oncology
Lena Peters, Ina Weidenfeld, Uwe Klemm, Anita Loeschcke, Robin Weihmann, Karl-Erich Jaeger, Thomas Drepper, Vasilis Ntziachristos, Andre C Stiel
Τhe morphology, physiology and immunology, of solid tumors exhibit spatial heterogeneity which complicates our understanding of cancer progression and therapy response. Understanding spatial heterogeneity necessitates high resolution in vivo imaging of anatomical and pathophysiological tumor information. We introduce Rhodobacter as bacterial reporter for multispectral optoacoustic (photoacoustic) tomography (MSOT). We show that endogenous bacteriochlorophyll a in Rhodobacter gives rise to strong optoacoustic signals >800 nm away from interfering endogenous absorbers...
March 13, 2019: Nature Communications
Xiaofeng Li, Wengui Xu
Impaired antitumor immunity or induced immunosuppression in the tumor microenvironment contributes significantly to tumor progression and resistance to immunotherapy. It is becoming increasingly recognized that dynamic metabolic programming orchestrates appropriate immune responses, whereas incorrect metabolic reprogramming may underlie aberrant immune remodeling. Furthermore, pathways that control cellular metabolism and immune cell function by transcriptional and post‑transcriptional mechanisms are intimately interlinked, including hypo-xia‑inducible factor 1α, c‑Myc and phosphatidylinositol 3‑kinase/protein kinase B/mammalian target of rapamycin signaling...
March 4, 2019: Oncology Reports
Federica Liotti, Nella Prevete, Giancarlo Vecchio, Rosa Marina Melillo
Tumors modulate the host immune cells within their microenvironment to avoid recognition and elimination by our immune system, a phenotype called cancer immune escape. Different mechanisms responsible for cancer immune escape that result either in decreased tumor immunogenicity or in increased tumor immunosuppressive activity have been identified. Recently, various immunotherapeutic approaches have been developed with the aim to revert tumor immune escape. The aims of this review are to explore the immunological aspects of thyroid cancer and to assess whether these features can be exploited in the prognosis and treatment of advanced forms of this disease...
2019: F1000Research
Connor J Dwyer, Hannah M Knochelmann, Aubrey S Smith, Megan M Wyatt, Guillermo O Rangel Rivera, Dimitrios C Arhontoulis, Eric Bartee, Zihai Li, Mark P Rubinstein, Chrystal M Paulos
Adoptive T cell transfer therapy (ACT) using tumor infiltrating lymphocytes or lymphocytes redirected with antigen receptors (CAR or TCR) has revolutionized the field of cancer immunotherapy. Although CAR T cell therapy mediates robust responses in patients with hematological malignancies, this approach has been less effective for treating patients with solid tumors. Additionally, toxicities post T cell infusion highlight the need for safer ACT protocols. Current protocols traditionally expand T lymphocytes isolated from patient tumors or from peripheral blood to large magnitudes in the presence of high dose IL-2 prior to infusion...
2019: Frontiers in Immunology
Narayanasamy Badrinath, So Young Yoo
Cancer stem cells (CSCs) are one of the reasons for the relapse of cancer cells and metastasis. They have drug resistance against most chemotherapeutic agents. CSCs are also responsible for tumor cell heterogeneity and cause minimal residual disease. In order to achieve complete regression of tumors, CSCs have to be targeted. Recent advances in immunotherapies have shown promising outcomes in curing cancer, which are also applicable to target CSCs. CSCs express immune markers and exhibit specific immune characteristics in various cancers, which can be used in immunotherapies to target CSCs in the tumor microenvironment...
March 5, 2019: Cancers
Dario Neri
The remarkable clinical success of immune-checkpoint inhibitors for the treatment of a growing number of cancer types has sparked interest in the discovery of novel forms of immunotherapy, which may be used alone or in combination. In this context, cytokine-based therapeutics are well poised to play a role in modern cancer therapy. This article focuses on antibody-cytokine fusion proteins (also called "immunocytokines") as one class of biopharmaceuticals that can substantially improve the therapeutic index and, thus, the applicability of cytokine products...
March 2019: Cancer Immunology Research
Alberto Salazar, Israel Casanova-Méndez, Michele Pacheco-Quito, Henry Velázquez-Soto, Julio Ayala-Balboa, Enrique O Graue-Hernández, Jeanet Serafín-López, María C Jiménez-Martínez
Allergic conjunctivitis (AC) is one of the most common ophthalmological disorders seen in clinical practice. Growing evidence from recent years suggests that a subset of IL-10-expressing B cells is involved in inflammatory allergic diseases. In this study, we aimed to evaluate the potential involvement of blood Bregs cells in perennial allergic conjunctivitis (PAC), and interleukins (IL)-1β, IL-6, IL-8, IL-10, and IL-12, and tumor necrosis factor (TNF)-α, were measured in tear samples and compared with healthy controls (HC) using flow cytometry...
February 27, 2019: International Journal of Molecular Sciences
Alexander C Huang, Robert J Orlowski, Xiaowei Xu, Rosemarie Mick, Sangeeth M George, Patrick K Yan, Sasikanth Manne, Adam A Kraya, Bradley Wubbenhorst, Liza Dorfman, Kurt D'Andrea, Brandon M Wenz, Shujing Liu, Lakshmi Chilukuri, Andrew Kozlov, Mary Carberry, Lydia Giles, Melanie W Kier, Felix Quagliarello, Suzanne McGettigan, Kristin Kreider, Lakshmanan Annamalai, Qing Zhao, Robin Mogg, Wei Xu, Wendy M Blumenschein, Jennifer H Yearley, Gerald P Linette, Ravi K Amaravadi, Lynn M Schuchter, Ramin S Herati, Bertram Bengsch, Katherine L Nathanson, Michael D Farwell, Giorgos C Karakousis, E John Wherry, Tara C Mitchell
Immunologic responses to anti-PD-1 therapy in melanoma patients occur rapidly with pharmacodynamic T cell responses detectable in blood by 3 weeks. It is unclear, however, whether these early blood-based observations translate to the tumor microenvironment. We conducted a study of neoadjuvant/adjuvant anti-PD-1 therapy in stage III/IV melanoma. We hypothesized that immune reinvigoration in the tumor would be detectable at 3 weeks and that this response would correlate with disease-free survival. We identified a rapid and potent anti-tumor response, with 8 of 27 patients experiencing a complete or major pathological response after a single dose of anti-PD-1, all of whom remain disease free...
February 25, 2019: Nature Medicine
Kota Iwahori, Yasushi Shintani, Soichiro Funaki, Yoko Yamamoto, Mitsunobu Matsumoto, Tetsuya Yoshida, Akiko Morimoto-Okazawa, Atsunari Kawashima, Eiichi Sato, Stephen Gottschalk, Meinoshin Okumura, Atsushi Kumanogoh, Hisashi Wada
Cancer immunotherapy, including immune checkpoint inhibitors, exerts beneficial effects in cancer patients. However, immune checkpoint inhibitors are only advantageous for a limited population of cancer patients. Therefore, companion diagnostics are needed in order to identify patients for whom these therapies are effective. In the present study, we evaluated detailed immunological aspects in clinical specimens from non-small cell lung cancer (NSCLC) patients. We analyzed the immune profiles, T cell cytotoxicity, and TCR repertoire of peripheral blood, normal lung tissue, and tumor tissue from NSCLC patients...
February 22, 2019: Scientific Reports
Qianwen Zhang, Yan Zhang, Yaqing Chen, Jianchang Qian, Xuesai Zhang, Ker Yu
PURPOSE: We aimed to investigate efficacy and mechanism of MTI-31 (LXI-15029), a novel mTORC1/mTORC2 inhibitor currently in human trial (NCT03125746), in non-small cell lung cancer (NSCLC) models of multiple driver mutations and tyrosine kinase inhibitor (TKI)-resistance. EXPERIMENTAL DESIGN: Gene depletion, inhibitor treatment, immunological, flow cytometry, cellular and animal studies were performed to determine in vitro and in vivo efficacy in NSCLC models of driver mutations and elucidate roles by mTOR-complexes in regulating migration, epithelial-mesenchymal transition (EMT), metastasis, intracranial tumor growth and immune-escape...
February 22, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Pan Pan, Yi-Wen Huang, Kiyoko Oshima, Martha Yearsley, Jianying Zhang, Mark Arnold, Jianhua Yu, Li-Shu Wang
Cancer is considered a fetal disease caused by uncontrolled proliferation and progression of abnormal cells. The most efficient cancer therapies suppress tumor growth, prevent progression and metastasis, and are minimally toxic to normal cells. Natural compounds have shown a variety of chemo-protective effects alone or in combination with standard cancer therapies. Along with better understanding of the dynamic interactions between our immune system and cancer development, nutritional immunology-the use of natural compounds as immunomodulators in cancer patients-has begun to emerge...
February 22, 2019: Critical Reviews in Food Science and Nutrition
Lin Kong, Jing Gao, Jiyi Hu, Rong Lu, Jing Yang, Xianxin Qiu, Weixu Hu, Jiade J Lu
BACKGROUND: Glioblastoma (GBM) is a highly virulent tumor of the central nervous system, with a median survival < 15 months. Clearly, an improvement in treatment outcomes is needed. However, the emergence of these malignancies within the delicate brain parenchyma and their infiltrative growth pattern severely limit the use of aggressive local therapies. The particle therapy represents a new promising therapeutic approach to circumvent these prohibitive conditions with improved treatment efficacy...
February 20, 2019: Cancer Communications
Zhen-Tao Zhang, Ming-Yi Huang-Fu, Wen-Hong Xu, Min Han
The tumor microenvironment is the cellular environment that is also described as the "soil" for supporting tumor growth, proliferation, invasion and metastasis, as well as protecting tumor cells from immunological recognition. Notably, tumor cells can grow much faster than other normal organs and invade surrounding tissues more easily, which results in abnormal expression of enzymes in the tumor microenvironment, including matrix metalloproteinases (MMPs), cathepsins, phospholipases, oxidoreductases, etc...
February 15, 2019: European Journal of Pharmaceutics and Biopharmaceutics
Shu-Hai Chen, Bing-Yuan Zhang, Bin Zhou, Cheng-Zhan Zhu, Le-Qi Sun, Yu-Jie Feng
Perineural invasion (PNI) can be found in a variety of malignant tumors. It is a sign of tumor metastasis and invasion and portends the poor prognosis of patients. The pathological description and clinical significance of PNI are clearly understood, but exploration of the underlying molecular mechanism is ongoing. It was previously thought that the low-resistance channel in the anatomic region led to the occurrence of PNI. However, with rapid development of precision medicine and molecular biology, we have gradually realized that the occurrence of PNI is not the result of a single factor...
2019: American Journal of Cancer Research
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