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tumor immunological microenvironment

Georg Aue, Clare Sun, Delong Liu, Jae-Hyun Park, Stefania Pittaluga, Xin Tian, Elinor Lee, Susan Soto, Janet Valdez, Irina Maric, Maryalice Stetler-Stevenson, Constance Yuan, Yusuke Nakamura, Pawel Muranski, Adrian Wiestner
Immune stimulation contributes to lenalidomide's antitumor activity. Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature, autoreactive B cells in secondary lymphoid tissues, blood, and bone marrow and progressive immune dysfunction. Previous studies in CLL indicated that lenalidomide can repair defective T cell function in vitro. Whether T cell activation is required for clinical response to lenalidomide remains unclear. In this study, we report changes in the immune microenvironment in patients with CLL treated with single-agent lenalidomide and associate the immunologic effects of lenalidomide with antitumor response...
August 13, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Ira Sharma, Avninder Singh, Fouzia Siraj, Sunita Saxena
BACKGROUND: Glioblastoma multiforme (GBM) is one of the lethal malignant tumors of the central nervous system. Despite advances made in understanding this complex disease, little has been achieved in improving clinical efficacy towards it. Factors such as chemokines play important role in shaping the tumor microenvironment which in turn plays a significant role in deciding course of tumor progression. In this study, we investigated the role of chemokine IL-8 in glioblastoma progression with particular emphasis on immunomodulation, cellular proliferation, invasion and vascular mimicry...
August 8, 2018: Journal of Biomedical Science
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 of vagus 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
Tyler A Herek, Jacob E Robinson, Tayla B Heavican, Catalina Amador, Javeed Iqbal, Christine E Cutucache
OBJECTIVE: Caveolin-1 (CAV1) is known for its role as both a tumor suppressor and an oncogene, harboring a highly context-dependent role within a myriad of malignancies and cell types. In an immunological context, dysregulation of CAV1 expression has been shown to alter immunological signaling functions and suggests a pivotal role for CAV1 in the facilitation of proper immune responses. Nonetheless, it is still unknown how Cav1-deficiency and heterozygosity would impact the development and composition of lymphoid organs in mice...
July 13, 2018: BMC Research Notes
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
Gareth J Morgan, Leo Rasche
Utilizing advances in genetic and immunologic analysis to segment and direct treatment is potentially a way of maintaining therapeutic progress toward cure in multiple myeloma (MM). This approach works well using clinical segments but can be optimized using recent genetic and immunologic technologies, which have opened the possibility of enhancing risk stratification and disease subclassification. Areas covered: This position paper discusses strategies to segment myeloma into subgroups with distinct risk profiles and distinct targetable lesions are presented...
July 2018: Expert Review of Hematology
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
Jared M Newton, Aurelie Hanoteau, Andrew G Sikora
The tumor immune microenvironment (TIME) has recently been recognized as a critical mediator of treatment response in solid tumors, especially for immunotherapies. Recent clinical advances in immunotherapy highlight the need for reproducible methods to accurately and thoroughly characterize the tumor and its associated immune infiltrate. Tumor enzymatic digestion and flow cytometric analysis allow broad characterization of numerous immune cell subsets and phenotypes; however, depth of analysis is often limited by fluorophore restrictions on panel design and the need to acquire large tumor samples to observe rare immune populations of interest...
June 7, 2018: Journal of Visualized Experiments: JoVE
Gabriella Emri, György Paragh, Ágnes Tósaki, Eszter Janka, Sándor Kollár, Csaba Hegedűs, Emese Gellén, Irén Horkay, Gábor Koncz, Éva Remenyik
Ultraviolet (UV) light is absorbed by nucleic acids, proteins or other endogenous chromophores, such as porphyrins, flavins and melanin, triggering biological processes in skin cells. Both UV-induced mutations in melanocytes and changes in the immune microenvironment are understood to play a role in the development of cutaneous melanoma. The degree of UV-induced stress and the protection against this stress are influenced by both intracellular and intercellular molecular interactions. The present review summarizes the known major molecular biological changes induced by UV light in the skin that play a role in melanoma initiation and promotion...
August 2018: Journal of Photochemistry and Photobiology. B, Biology
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
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