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cancer immunological microenvironment

Jonas Steenbrugge, Koen Breyne, Kristel Demeyere, Olivier De Wever, Niek N Sanders, Wim Van Den Broeck, Cecile Colpaert, Peter Vermeulen, Steven Van Laere, Evelyne Meyer
BACKGROUND: Murine breast cancer models relying on intraductal tumor cell inoculations are attractive because they allow the study of breast cancer from early ductal carcinoma in situ to metastasis. Using a fully immunocompetent 4T1-based intraductal model for triple-negative breast cancer (TNBC) we aimed to investigate the immunological responses that guide such intraductal tumor progression, focusing on the prominent role of macrophages. METHODS: Intraductal inoculations were performed in lactating female mice with luciferase-expressing 4T1 mammary tumor cells either with or without additional RAW264...
August 15, 2018: Journal of Experimental & Clinical Cancer Research: CR
Yutaka Kawakami
Clinical trials for immune-checkpoint inhibitors and T cell-based adoptive cell therapy have demonstrated robust clinical responses in some patients with advanced cancer of various types, including hematological malignancies. However, response rates to PD-1/PD-L1 blockade are about 10%-30% in most cancer types. To improve the efficacy of immunotherapy, combination immunotherapy using other standard cancer therapies (e.g., chemotherapy, target therapy, and radiation) and various immune modulators for crucial regulation points in antitumor T-cell responses (e...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Eva Reijmen, Luca Vannucci, Marijke De Couck, Jacques De Grève, Yori Gidron
Accumulating evidence points to a beneficial effect ofvagus nerve activity in tumor development. The vagus nerve is proposed to slow tumorigenesis because of its anti-inflammatory properties mediated through ACh and the α7nAChR. Since α7nAChRs are widely expressed by many types of immune cells we hypothesized that the vagus nerve affects the tumor microenvironment and anticancer immunity. We found direct evidence in studies using animal cancer models that vagus nerve stimulation alters immunological responses relevant to the tumor microenvironment...
August 2, 2018: Immunology Letters
Yuan Zhuang, Sihan Li, Huihui Wang, Jingbo Pi, Yuhui Xing, Guang Li
PURPOSE: It has become increasingly clear in cancer treatment that radiotherapy can be enhanced by immunotherapy. In the present study, we evaluated a novel triple combination therapy consisting of local radiotherapy, intratumoral CpG, and systemic PD-1 blockade in lung cancer models. METHODS: The efficacy of a novel triple therapy was examined by recording tumor volume and survival time. The immunologic effects of this novel triple therapy were evaluated by the frequency and percentage of immune cells and cytokines using flow cytometry...
August 3, 2018: Journal of Cancer Research and Clinical Oncology
Aras Toker, Linh T Nguyen, Simone C Stone, Cindy Yang, Sarah R Katz, Patricia A Shaw, Blaise A Clarke, Danny A Ghazarian, Ayman S Al Habeeb, Alexandra M Easson, Wey Leong, David McCready, Michael Reedijk, Cynthia J Guidos, Trevor J Pugh, Marcus Q Bernardini, Pamela S Ohashi
PURPOSE: Regulatory T (Treg) cells expressing the transcription factor FOXP3 are essential for the maintenance of immunological self-tolerance but play a detrimental role in most cancers due to their ability to suppress antitumor immunity. The phenotype of human circulating Treg cells has been extensively studied, but less is known about tumor-infiltrating Treg cells. We studied the phenotype and function of tumor-infiltrating Treg cells in ovarian cancer and melanoma to identify potential Treg cell-associated molecules that can be targeted by tumor immunotherapies...
July 31, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Juan-Luis Blazquez, Audrey Benyamine, Christine Pasero, Daniel Olive
Recent findings in the immunology field have pointed out the emergent role of butyrophilins/butyrophilin-like molecules (BTN/BTNL in human, Btn/Btnl in mouse) in the modulation of γδ T cells. As long as the field develops exponentially, new relationships between certain γδ T cell subsets, on one hand, and their BTN/BTNL counterparts mainly present on epithelial and tumor cells, on the other, are described in the scientific literature. Btnl1/Btnl6 in mice and BTNL3/BTNL8 in humans regulate the homing and maturation of Vγ7+ and Vγ4+ T cells to the gut epithelium...
2018: Frontiers in Immunology
Dana Mitchell, Sreenivasulu Chintala, Mahua Dey
Plasmacytoid dendritic cells (pDCs) comprise a subset of dendritic cells characterized by their ability to produce large amount of type I interferon (IFN-I/α). Originally recognized for their role in modulating immune responses to viral stimulation, growing interest has been directed toward their contribution to tumorigenesis. Under normal conditions, Toll-like receptor (TLR)-activated pDCs exhibit robust IFN-α production and promote both innate and adaptive immune responses. In cancer, however, pDCs demonstrate an impaired response to TLR7/9 activation, decreased or absent IFN-α production and contribute to the establishment of an immunosuppressive tumor microenvironment...
September 15, 2018: Journal of Neuroimmunology
Dimitra Kerdidani, Sophia Magkouta, Panagiotis Chouvardas, Vassiliki Karavana, Konstantinos Glynos, Fani Roumelioti, Spyros Zakynthinos, Els Wauters, Wim Janssens, Diether Lambrechts, George Kollias, Maria Tsoumakidou
Chronic obstructive pulmonary disease is a chronic inflammatory disorder with an increased incidence of lung cancer. The emphysema component of chronic obstructive pulmonary disease confers the greatest proportion to lung cancer risk. Although tumors create inflammatory conditions to escape immunity, the immunological responses that control growth of nascent cancer cells in pre-established inflammatory microenvironments are unknown. In this study, we addressed this issue by implanting OVA-expressing cancer cells in the lungs of mice with cigarette smoke-induced emphysema...
July 23, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Angelica Silva-Figueroa, Pamela Villalobos, Michelle D Williams, Roland L Bassett, Callisia N Clarke, Jeffrey E Lee, Naifa L Busaidy, Nancy D Perrier
BACKGROUND: Four distinct tumor microenvironments have been proposed based on the expression of programmed death-ligand 1 and the presence of tumor-infiltrating lymphocytes: immunotype I (adaptive resistance, tumor-infiltrating lymphocytes+ and programmed death-ligand 1+); immunotype II (immunologic ignorance, tumor-infiltrating lymphocytes- and programmed death-ligand 1-); immunotype III (intrinsic induction; tumor-infiltrating lymphocytes- and programmed death-ligand 1+); and immunotype IV (tolerance, tumor-infiltrating lymphocytes+ and programmed death-ligand 1-)...
July 19, 2018: Surgery
Xiaopin Duan, Christina Chan, Wenbin Lin
Cancer immunotherapies by training or stimulating the inherent immunological systems to recognize, attack, and eradicate tumor cells with minimal damage to healthy cells have demonstrated promising clinical responses in recent years. However, most of these immunotherapeutic strategies only benefit a small subset of patients and cause systemic autoimmune side effects in some patients. Immunogenic cell death (ICD)-inducing modalities not only directly kill cancer cells, but also induce antitumor immune responses against a broad spectrum of solid tumors...
July 17, 2018: Angewandte Chemie
Todd A Triplett, Kendra C Garrison, Nicholas Marshall, Moses Donkor, John Blazeck, Candice Lamb, Ahlam Qerqez, Joseph D Dekker, Yuri Tanno, Wei-Cheng Lu, Christos S Karamitros, Kyle Ford, Bing Tan, Xiaoyan M Zhang, Karen McGovern, Silvia Coma, Yoichi Kumada, Mena S Yamany, Enrique Sentandreu, George Fromm, Stefano Tiziani, Taylor H Schreiber, Mark Manfredi, Lauren I R Ehrlich, Everett Stone, George Georgiou
Increased tryptophan (Trp) catabolism in the tumor microenvironment (TME) can mediate immune suppression by upregulation of interferon (IFN)-γ-inducible indoleamine 2,3-dioxygenase (IDO1) and/or ectopic expression of the predominantly liver-restricted enzyme tryptophan 2,3-dioxygenase (TDO). Whether these effects are due to Trp depletion in the TME or mediated by the accumulation of the IDO1 and/or TDO (hereafter referred to as IDO1/TDO) product kynurenine (Kyn) remains controversial. Here we show that administration of a pharmacologically optimized enzyme (PEGylated kynureninase; hereafter referred to as PEG-KYNase) that degrades Kyn into immunologically inert, nontoxic and readily cleared metabolites inhibits tumor growth...
September 2018: Nature Biotechnology
Shou-Sheng Liu, Yuan-Zhong Yang, Chang Jiang, Qi Quan, Qian-Kun Xie, Xiao-Pai Wang, Wen-Zhuo He, Yu-Ming Rong, Ping Chen, Qiong Yang, Lin Yang, Bei Zhang, Xiao-Jun Xia, Peng-Fei Kong, Liang-Ping Xia
BACKGROUND: Currently, mismatch repair-deficient (dMMR) status is a promising candidate for targeted immune checkpoint inhibition therapy in colorectal cancer (CRC) patients, however, the potential immunological mechanism has not yet been well clarified and some other predictors need to be excavated as well. METHODS: We collected 330 CRC patients by the match of mismatch repair-proficient (167) and dMMR (163), explored the relationship between MMR status and some important immune molecules including MHC class I, CD3, CD4, CD8, CD56, programmed death-1 and programmed death ligand-1, and investigated the risk factors for dMMR status as well as low MHC class I expression...
July 13, 2018: Journal of Translational Medicine
Jamie Honeychurch, Timothy M Illidge
In addition to tumouricidal activity, radiotherapy is now recognized to display potent immunostimulatory properties that can contribute to the generation of anti-cancer immune responses. Treatment with radiation can induce a variety of pro-immunogenic and phenotypic changes in malignant cells, and recalibrate the immune contexture of the tumour microenvironment, leading to enhanced activation of the innate immune system, and priming of tumour-specific T-cell immunity. The immune-dependent effects of radiotherapy provide a sound rationale for the development of combination strategies, whereby the immunomodulatory properties of radiation can be exploited to augment the activity of immunotherapeutic agents...
December 2017: Therapeutic advances in vaccines and immunotherapy
Sivan Izraely, Shlomit Ben-Menachem, Orit Sagi-Assif, Alona Telerman, Inna Zubrilov, Ofir Ashkenazi, Tsipi Meshel, Shelly Maman, Javier I J Orozco, Matthew P Salomon, Diego M Marzese, Metsada Pasmanik-Chor, Eli Pikarsky, Marcelo Ehrlich, Dave S B Hoon, Isaac P Witz
Melanoma has the highest propensity to metastasize to the brain compared to other cancers, as brain metastases are found frequently high in patients who have prolonged survival with visceral metastasis. Once disseminated in the brain, melanoma cells communicate with brain resident cells that include astrocytes and microglia. Microglia cells are the resident macrophages of the brain, and are the main immunological cells in the CNS involved in neuroinflammation. Data on the interactions between brain metastatic melanoma cells and microglia and on the role of microglia-mediated neuroinflammation in facilitating melanoma brain metastasis is lacking...
July 11, 2018: International Journal of Cancer. Journal International du Cancer
Frank Stenner, Christoph Renner
Follicular lymphoma (FL) is the most frequent indolent lymphoma in the Western world and is characterized in almost all cases by the t(14;18) translocation that results in overexpression of BCL2, an anti-apoptotic protein. The entity includes a spectrum of subentities that differ from an indolent to a very aggressive growth pattern. As a consequence, treatment can include watch & wait up to intensive chemotherapy including allogeneic stem cell transplantation. The immune cell microenvironment has been recognized as a major driver of outcome of FL patients and gene expression profiling has identified a clinically relevant gene expression signature that classifies an immune response to the lymphoma cells...
2018: Frontiers in Oncology
Neeraj Bhalla, Rachel Brooker, Michael Brada
Immunotherapy has become standard of care in advanced non-small cell lung cancer (NSCLC) in a number of settings. Radiotherapy remains an important and potentially curative treatment for localized and locally advanced NSCLC not amenable to surgery. While the principal cytotoxic effect of ionizing radiation is via DNA damage, the effect on tumour microenvironment, promoting dendritic cell presentation of tumour-derived antigens to T cells stimulating the host adaptive immune system to mount an immune response against tumours cells, has become of particular interest when combining immunomodulating agents with radiation...
May 2018: Journal of Thoracic Disease
Emma V Morris, Claire M Edwards
Obesity has become a global epidemic influencing the establishment and progression of a wide range of diseases, such as diabetes, cardiovascular disease, and cancer. In 2016, International Agency for Research on Cancer reported that obesity is now associated with 13 different cancers, one of which is multiple myeloma (MM), a destructive cancer of plasma cells that predominantly reside in the bone marrow. Obesity is the accumulation of excess body fat, which causes metabolic, endocrine, immunologic, and inflammatory-like changes...
June 26, 2018: Journal of Cellular Physiology
Sarah Rosanne Ottenhof, Rosa Sanne Djajadiningrat, Helene Hoegsbro Thygesen, Pamela Josephine Jakobs, Katarzyna Jóźwiak, Anne Marijne Heeren, Jeroen de Jong, Joyce Sanders, Simon Horenblas, Ekaterina Straschimirova Jordanova
The host's immune system plays a pivotal role in many tumor types, including squamous cell carcinomas (SCCs). We aim to identify immunological prognosticators for lymph node metastases (LNM) and disease-specific survival (DSS) in penile SCC. For this retrospective observational cohort study, penile SCC patients ( n  = 213) treated in the Netherlands Cancer Institute, were selected if sufficient formalin-fixed, paraffin-embedded tumor material was available. Analysis included previously described high-risk human papilloma virus (hrHPV) status, immunohistochemical scores for classical and non-classical human leukocyte antigen (HLA) class I, programmed death ligand-1 (PD-L1) expression, and novel data on tumor-infiltrating macrophages and cytotoxic an regulatory T-cells...
2018: Frontiers in Immunology
Joe Pelt, Sara Busatto, Mauro Ferrari, E Aubrey Thompson, Kabir Mody, Joy Wolfram
Clinically approved cancer therapies include small molecules, antibodies, and nanoparticles. There has been major progress in the treatment of several cancer types over recent decades. However, many challenges remain for optimal use of conventional and nanoparticle-based therapies in oncology including poor drug delivery, rapid clearance, and drug resistance. The antimalarial agent chloroquine has been found to mitigate some of these challenges by modulating cancer cells and the tissue microenvironment. Particularly, chloroquine was recently found to reduce immunological clearance of nanoparticles by resident macrophages in the liver, leading to increased tumor accumulation of nanodrugs...
June 20, 2018: Pharmacology & Therapeutics
Nana H Overgaard, Daniel R Principe, Kyle M Schachtschneider, Jeanne Toft Jakobsen, Laurie A Rund, Paul J Grippo, Lawrence B Schook, Gregers Jungersen
In recent years, immunotherapy has shown considerable promise in the management of several malignancies. However, the majority of preclinical studies have been conducted in rodents, the results of which often translate poorly to patients given the substantial differences between murine and human immunology. As the porcine immune system is far more analogous to that of humans, pigs may serve as a supplementary preclinical model for future testing of such therapies. We have generated the genetically modified Oncopig with inducible tumor formation resulting from concomitant KRASG12D and TP53R167H mutations under control of an adenoviral vector Cre-recombinase (AdCre)...
2018: Frontiers in Immunology
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