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Tumor immune recognition

Elizabeth S Nakasone, Sara A Hurvitz, Kelly E McCann
Breast cancer is the most prevalent malignancy in women and the second most common cause of cancer-related death worldwide. Despite major innovations in early detection and advanced therapeutics, up to 30% of women with node-negative breast cancer and 70% of women with node-positive breast cancer will develop recurrence. The recognition that breast tumors are infiltrated by a complex array of immune cells that influence their development, progression, and metastasis, as well as their responsiveness to systemic therapies has sparked major interest in the development of immunotherapies...
2018: Drugs in Context
Baixin Ye, Creed M Stary, Xuejun Li, Qingping Gao, Chunsheng Kang, Xiaoxing Xiong
Intratumor heterogeneity of tumor clones and an immunosuppressive microenvironment in cancer ecosystems contribute to inherent difficulties for tumor treatment. Recently, chimeric antigen receptor (CAR) T-cell therapy has been successfully applied in the treatment of B-cell malignancies, underscoring its great potential in antitumor therapy. However, functional challenges of CAR-T cell therapy, especially in solid tumors, remain. Here, we describe cancer-immunity phenotypes from a clonal-stromal-immune perspective and elucidate mechanisms of T-cell exhaustion that contribute to tumor immune evasion...
February 15, 2018: Molecular Cancer
Zhaowei Chen, Quanyin Hu, Zhen Gu
Cell therapy has become a momentum-gathering treatment strategy for a variety of diseases, including cancer, diabetes, hemophilia, and cardiomyopathy. However, clinical applications of conventional cell therapies have often been compromised by rapid decline in viability and function of the transplanted cells due to host recognition and subsequent foreign body rejection. Along this line, cell engineering technologies such as cell encapsulation within microcapsules and immobilization in porous scaffolds have been implemented to address the immunosuppression concerns...
February 15, 2018: Accounts of Chemical Research
Flavia Radogna, Marc Diederich
Cancer is evading the host's defense mechanisms leading to avoidance of immune destruction. During tumor progression, immune-evading cancer cells arise due to selective pressure from the hypoxic and nutrient-deprived microenvironment. Thus, therapies aiming at re-establishing immune destruction of pathological cells constitute innovating anti-cancer strategies. Accumulating evidence suggests that selected conventional chemotherapeutic drugs increase the immunogenicity of stressed and dying cancer cells by triggering a form of cell death called immunogenic cell death (ICD), which is characterized by the release of danger-associated molecular patterns (DAMPs)...
February 10, 2018: Biochemical Pharmacology
Anastasiia Filippova, Julie Charles, Olivier Epaulard, Raphaële Germi, Virginie Persoons, Isabelle Templier, Marie-Therese Leccia, Brigitte Dreno, Irina Malova, Patrice Morand, Julien Lupo
Exogenous human herpes virus 6 (HHV-6) reinfection has never been reported in patients receiving tumor-infiltrating T lymphocytes therapy. We report an unusual case of HHV-6 infection following infusion of HHV-6 infected autologous T lymphocytes. HHV-6 infection could interfere with the tumor antigen immune recognition and the efficacy of immunotherapy.
February 9, 2018: Cytotherapy
Margarita Udall, Maria Rizzo, Juliet Kenny, Jim Doherty, SueAnn Dahm, Paul Robbins, Eric Faulkner
BACKGROUND: The programmed death receptor 1 (PD-1) protein is a cell-surface receptor on certain lymphocytes that, with its ligand programmed death ligand 1 (PD-L1), helps to down-regulate immune responses. Many cancer types express PD-L1 and evade immune recognition via the PD-1/PD-L1 interaction. Precision therapies targeting the PD-1/PD-L1 pathway have the potential to improve response and thereby offer a novel treatment avenue to some patients with cancer. However, this new therapeutic approach requires reliable methods for identifying patients whose cancers are particularly likely to respond...
February 9, 2018: Diagnostic Pathology
Cecilia Garlanda, Barbara Bottazzi, Elena Magrini, Antonio Inforzato, Alberto Mantovani
Innate immunity includes a cellular and a humoral arm. PTX3 is a fluid-phase pattern recognition molecule conserved in evolution which acts as a key component of humoral innate immunity in infections of fungal, bacterial, and viral origin. PTX3 binds conserved microbial structures and self-components under conditions of inflammation and activates effector functions (complement, phagocytosis). Moreover, it has a complex regulatory role in inflammation, such as ischemia/reperfusion injury and cancer-related inflammation, as well as in extracellular matrix organization and remodeling, with profound implications in physiology and pathology...
April 1, 2018: Physiological Reviews
Chuanjie Qin, Quan Gong, Zhengyong Wen, Dengyue Yuan, Ting Shao, Huatao Li
Toll-like receptor 5 (TLR5) is an important pathogen recognition receptor (PRR) that recognizes the flagellin protein of pathogenic bacteria and plays a fundamental role in activating the innate immune response. In this study, full-length pvTLR5m (membrane) and pvTLR5s (soluble) genes were cloned from darkbarbel catfish Pelteobagrus vachellii, and their expression and that of downstream genes were analyzed following exposure to the Aeromonas hydrophila pathogen. The 3009 bp pvTLR5m cDNA includes a 2652 bp open reading frame (ORF) encoding 884 amino acids...
February 2, 2018: Fish & Shellfish Immunology
Aurélie Durgeau, Yasemin Virk, Stéphanie Corgnac, Fathia Mami-Chouaib
Recent advances in cancer treatment have emerged from new immunotherapies targeting T-cell inhibitory receptors, including cytotoxic T-lymphocyte associated antigen (CTLA)-4 and programmed cell death (PD)-1. In this context, anti-CTLA-4 and anti-PD-1 monoclonal antibodies have demonstrated survival benefits in numerous cancers, including melanoma and non-small-cell lung carcinoma. PD-1-expressing CD8+ T lymphocytes appear to play a major role in the response to these immune checkpoint inhibitors (ICI). Cytotoxic T lymphocytes (CTL) eliminate malignant cells through recognition by the T-cell receptor (TCR) of specific antigenic peptides presented on the surface of cancer cells by major histocompatibility complex class I/beta-2-microglobulin complexes, and through killing of target cells, mainly by releasing the content of secretory lysosomes containing perforin and granzyme B...
2018: Frontiers in Immunology
Tiphaine Delaunay, Mathilde Violland, Nicolas Boisgerault, Soizic Dutoit, Virginie Vignard, Christian Münz, Monique Gannage, Brigitte Dréno, Kristine Vaivode, Dace Pjanova, Nathalie Labarrière, Yaohe Wang, E Antonio Chiocca, Fabrice Le Boeuf, John C Bell, Philippe Erbs, Frédéric Tangy, Marc Grégoire, Jean-François Fonteneau
Oncolytic immunotherapy using oncolytic viruses (OV) has been shown to stimulate the antitumor immune response by inducing the release of tumor-associated antigens (TAA) and danger signals from the dying infected tumor cells. In this study, we sought to determine if the lysis of tumor cells induced by different OV: measles virus, vaccinia virus, vesicular stomatitis virus, herpes simplex type I virus, adenovirus or enterovirus, has consequences on the capacity of tumor cells to present TAA, such as NY-ESO-1...
2018: Oncoimmunology
Jeroen F Vermeulen, Wim Van Hecke, Elisabeth J M Adriaansen, Mieke K Jansen, Rianne G Bouma, José Villacorta Hidalgo, Paul Fisch, Roel Broekhuizen, Wim G M Spliet, Marcel Kool, Niels Bovenschen
Pediatric medulloblastomas are the most frequently diagnosed embryonal tumors of the central nervous system. Current therapies cause severe neurological and cognitive side effects including secondary malignancies. Cellular immunotherapy might be key to improve survival and to avoid morbidity. Efficient killing of tumor cells using immunotherapy requires to overcome cancer-associated strategies to evade cytotoxic immune responses. Here, we examined the immune response and immune evasion strategies in pediatric medulloblastomas...
2018: Oncoimmunology
Elien M Doorduijn, Marjolein Sluijter, Koen A Marijt, Bianca J Querido, Sjoerd H van der Burg, Thorbald van Hall
Cancers frequently evade immune-recognition by lowering peptide:MHC-I complexes on their cell surface. Limited peptide supply due to TAP-deficiency results in such MHC-Ilow immune-escape variants. Previously, we reported on a category of TAP-independent self-peptides, called TEIPP, with selective presentation by these tumors. Here we demonstrate that in contrast to T cells specific for conventional tumor antigens, TEIPP-directed T cells remain naïve in mice bearing immune-escaped tumors. This unaffected state was caused by low levels of MHC-I on the tumors and the failure to cross-present low levels of antigenic protein by host APCs...
2018: Oncoimmunology
Marian C Okondo, Sahana D Rao, Cornelius Y Taabazuing, Ashley J Chui, Sarah E Poplawski, Darren C Johnson, Daniel A Bachovchin
Val-boroPro (PT-100, Talabostat) induces powerful anti-tumor immune responses in syngeneic cancer models, but its mechanism of action has not yet been established. Val-boroPro is a non-selective inhibitor of post-proline-cleaving serine proteases, and the inhibition of the highly related cytosolic serine proteases Dpp8 and Dpp9 (Dpp8/9) by Val-boroPro was recently demonstrated to trigger an immunostimulatory form of programmed cell death known as pyroptosis selectively in monocytes and macrophages. Here we show that Dpp8/9 inhibition activates the inflammasome sensor protein Nlrp1b, which in turn activates pro-caspase-1 to mediate pyroptosis...
January 26, 2018: Cell Chemical Biology
Bryce LaFoya, Jordan A Munroe, Alison Miyamoto, Michael A Detweiler, Jacob J Crow, Tana Gazdik, Allan R Albig
The traditional view of integrins portrays these highly conserved cell surface receptors as mediators of cellular attachment to the extracellular matrix (ECM), and to a lesser degree, as coordinators of leukocyte adhesion to the endothelium. These canonical activities are indispensable; however, there is also a wide variety of integrin functions mediated by non-ECM ligands that transcend the traditional roles of integrins. Some of these unorthodox roles involve cell-cell interactions and are engaged to support immune functions such as leukocyte transmigration, recognition of opsonization factors, and stimulation of neutrophil extracellular traps...
February 2, 2018: International Journal of Molecular Sciences
Dan Zhou, Yun Zhu, Min-Zhi Ouyang, Ming Zhang, Kui Tang, Cheng-Cheng Niu, Ling Li
Toll-like receptor 4 (TLR4) is a transmembrane pattern‑recognition receptor expressed in immune cells and the heart. Activation of TLR4 signaling during sepsis results in the release of cardiac depression mediators that may impair heart function. The present study aimed to determine whether TLR4 contributes to development of severe sepsis‑induced myocardial dysfunction. A cecum ligation and puncture (CLP) procedure was employed to establish severe sepsis models. Wild type (WT) and TLR4 knock‑out (TLR4‑KO) mice were divided into four groups: WT‑sham, TLR4‑KO‑sham, WT‑CLP, and TLR4‑KO‑CLP...
January 25, 2018: Molecular Medicine Reports
Jessica da Gama Duarte, Katherine Woods, Miles C Andrews, Andreas Behren
Within the immune system multiple mechanisms balance the need for efficient pathogen recognition and destruction with the prevention of tissue damage by excessive, inappropriate or even self-targeting (auto)immune reactions. This immune homeostasis is a tightly regulated system which fails during tumor development, often due to the hijacking of its essential self-regulatory mechanisms by cancer cells. It is facilitated not only by tumor intrinsic properties, but also by the microbiome, host genetics and other factors...
February 2, 2018: Immunology and Cell Biology
Dayana B Rivadeneira, Greg M Delgoffe
With the rapid rise of immunotherapy for cancer treatment, attention has focused on gaining a better understanding of T cell biology in the tumor microenvironment.  Elucidating the factors underlying changes in their function will allow for the development of new therapeutic strategies that could expand the patient population benefiting from immunotherapy, as well as circumvent therapy resistance. Cancers go beyond avoiding immune recognition and inducing T cell dysfunction through co-inhibitory molecules...
January 31, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
N Koyama, O Iwase, E Nakashima, K Kishida, T Kondo, Y Watanabe, H Takahashi, Y Umebayashi, Y Ogawa, H Miura
BACKGROUND: Nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody used as an immune checkpoint inhibitor, is commonly employed for its anti-tumor effects against various types of malignant tumors. However, its administration is complicated by immune-related adverse events (irAEs), including pneumonitis. CASE PRESENTATION: We present a case series of four patients with malignant melanoma, non-small cell lung cancer, and hypopharyngeal carcinoma who demonstrated pneumonitis induced by nivolumab, and further review clinicopathological characteristics of these patients in comparison with those of previously reported patients with nivolumab-induced pneumonitis...
January 30, 2018: BMC Pulmonary Medicine
Chu Lin, Jun Zhang
Natural killer (NK) cells are an important subset of lymphocytes which play a critical role in host immunity against cancer. With MHC-independent recognition, short lifespan and potent cytotoxicity, NK cells make a promising candidate for chimeric antigen receptor (CAR)-engineered cancer immunotherapy. Due to innate biological properties of NK cells, CAR-NK may outperform CAR-T therapy in terms of less side effects and more universal access, which may become a great reformation in CAR-based cancer immunotherapy...
January 26, 2018: Biochimica et Biophysica Acta
ZeNan L Chang, Michael H Lorenzini, Ximin Chen, Uyen Tran, Nathanael J Bangayan, Yvonne Y Chen
Chimeric antigen receptor (CAR)-expressing T cells targeting surface-bound tumor antigens have yielded promising clinical outcomes, with two CD19 CAR-T cell therapies recently receiving FDA approval for the treatment of B-cell malignancies. The adoption of CARs for the recognition of soluble ligands, a distinct class of biomarkers in physiology and disease, could considerably broaden the utility of CARs in disease treatment. In this study, we demonstrate that CAR-T cells can be engineered to respond robustly to diverse soluble ligands, including the CD19 ectodomain, GFP variants, and transforming growth factor beta (TGF-β)...
January 29, 2018: Nature Chemical Biology
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