Jiao Lu, Xiaoying Wang, Zhihao Feng, Yucheng Chen, Diguang Wen, Zuojin Liu
BACKGROUND: Liver ischaemia-reperfusion injury (IRI) is a major complication in the perioperative period and often leads to liver failure and even systemic inflammation. Sufficient evidence has demonstrated that isoflurane has anti-inflammatory effects. We aimed to determine whether isoflurane pretreatment protects against liver IRI and to investigate the mechanisms involved in this protection. METHODS: Male C57BL/6 mice were pretreated with or without isoflurane and subjected to 90 min of 70% liver ischaemia, followed by reperfusion for 6 h...
July 28, 2021: International Immunopharmacology
Dandan Song, Haoyu Lyu, Qiushi Feng, Jiangti Luo, Lin Li, Xiaosheng Wang
Although head and neck squamous cell cancer (HNSCC) is one of the cancer types in which immune checkpoint inhibitors (ICIs) has achieved a certain success, only a subset of HNSCC patients respond to ICIs. Thus, identification of HNSCC subtypes responsive to ICIs is crucial. Using hierarchical clustering, we identified three subtypes of HNSCC, termed Immunity-H, Immunity-M, and Immunity-L, based on the enrichment scores of 28 immune cells generated by the single-sample gene-set enrichment analysis of transcriptome data...
July 28, 2021: International Immunopharmacology
Jiawei Ji, Yuan Zhuang, Haozhou Wang, Chang Feng, Yong Zhao, Xiaodong Zhang
OBJECTIVE: Regulatory macrophages (Mregs) are a group of heterogeneous macrophages. These cells could induce immunosuppressive effects through the expression of immune regulatory molecules and cytokines. METHODS: The differentiation of Mregs was induced by treating bone marrow cells with M-CSF and prostratin in vitro. The cell-phenotypes and immunosuppressive function were determined by flow cytometry. Rt-PCR was employed to assess the mechanisms of Mregs. Skin grafted mouse model was used for in vivo validation...
July 28, 2021: International Immunopharmacology
Bregje M Koomen, Quirinus J M Voorham, Chantal C H J Epskamp-Kuijpers, Carmen van Dooijeweert, Anne S R van Lindert, Ivette A G Deckers, Stefan M Willems
OBJECTIVES: Immunohistochemical expression of programmed death-ligand 1 (PD-L1) is used as a predictive biomarker for prescription of immunotherapy to non-small cell lung cancer (NSCLC) patients. Accurate assessment of PD-L1 expression is therefore crucial. In this study, the extent of interlaboratory variation in PD-L1 positivity in the Netherlands was assessed, using real-world clinical pathology data. MATERIALS AND METHODS: Data on all NSCLC patients in the Netherlands with a mention of PD-L1 testing in their pathology report from July 2017 to December 2018 were extracted from PALGA, the nationwide network and registry of histo- and cytopathology in the Netherlands...
July 22, 2021: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Ryan J Shirey, Lewis D Turner, Luke L Lairson, Kim D Janda
PLD3 and PLD4 have recently been revealed to be endosomal exonucleases that regulate the innate immune response by digesting the ligands of nucleic acid sensors. These enzymes can suppress RNA and DNA innate immune sensors like toll-like receptor 9, and PLD4-deficent mice exhibit inflammatory disease. Targeting these immunoregulatory enzymes presents an opportunity to indirectly regulate innate immune nucleic acid sensors that could yield immunotherapies, adjuvants, and nucleic acid drug stabilizers. To aid in delineating the therapeutic potential of these targets, we have developed a high-throughput fluorescence enzymatic assay to identify modulators of PLD3 and PLD4...
July 28, 2021: Bioorganic & Medicinal Chemistry Letters
Shuang Wang, Xiaoming Hu, Wei Wei, Guanghui Ma
Immunotherapy that utilizes the human immune system to fight cancer represents a revolutionary method for cancer treatment. Immunotherapeutic agents that trigger the immune response should be carefully delivered to the desired site to maximize immunotherapy effectiveness and minimize side effects. Vesicles offer the possibility of encapsulating both hydrophilic and hydrophilic drugs and thus serve as a promising delivery tool. As multiple irreconcilable requirements exist at different transport stages, developing vesicles transformable in response to given stimuli is of great significance...
July 28, 2021: Advanced Drug Delivery Reviews
Holly Maulhardt, Alyson Marin, Holly Hesseltine, Gere diZerega
We describe here characterization of the response of local and metastatic disease and immunomodulation following intratumoral (IT) injection of submicron particle docetaxel (SPD) administered alone or in combination with systemic antibody anti-mCTLA-4 (anti-mCTLA-4) in the metastatic 4T1-Luc2-1A4 (4T1) murine breast cancer model. In-life assessments of treatment tolerance, tumor volume (TV), and metastasis were performed (n = 10 animals/group). At study end, immune cell populations in tumor-site tissues and peripheral blood were analyzed using flow cytometry...
July 31, 2021: Medical Oncology
Jochim Reinert, Antonia Beitzen-Heineke, Klaus Wethmar, Matthias Stelljes, Walter Fiedler, Stefan Schwartz
Treatment options for relapsed or refractory B-lymphoblastic leukaemia (r/r B-ALL) are limited and the prognosis of these patients remains dismal, but novel immunotherapeutic options such as the anti-CD22 antibody-drug-conjugate Inotuzumab-Ozogamicin (InO) have improved outcomes in these patients. Flow cytometry is essential to assess antigen-expression prior to treatment initiation of antigen-directed immunotherapies. Here, we present flow cytometric and clinical data of three adult patients with r/r B-ALL who failed treatment with InO associated with reduced or lost antigen-expression...
July 31, 2021: Annals of Hematology
Feiyang Cai, Shiyi Li, Hui Huang, Javed Iqbal, Canran Wang, Xing Jiang
Immune responses are involved in the pathogenesis of many diseases, including cancer, autoimmune diseases, and chronic inflammation. These responses are attributed to immune cells that produce cytokines, mediate cytotoxicity, and synthesize antibodies. Gold nanoparticles (GNPs) are novel agents that intervene with immune responses because of their unique physical-chemical properties. In particular, GNPs enhance anti-tumour activity during immunotherapy and eliminate excessive inflammation in autoimmune diseases...
July 31, 2021: Journal of Biomedical Materials Research. Part A
Rory Beattie, Katarzyna Furrer, Daniel P Dolan, Alessandra Curioni-Fontecedro, Daniel N Lee, Thomas Frauenfelder, Sylvia Hoeller, Walter Weder, Raphael Bueno, Isabelle Opitz, Scott Swanson
OBJECTIVES: Recent trials have begun to explore immune checkpoint inhibitors for non-small cell lung cancer in the neoadjuvant setting, but data on tumour response and surgical outcome remain limited. METHODS: Retrospective evaluation of clinical data from patients with non-small cell lung cancer treated with immune checkpoint inhibitors followed by lung resection was performed at 2 large volume institutions (1 North American, 1 European). Data were analysed using Chi-squared, Fisher's and Wilcoxon rank-sum tests where appropriate...
July 31, 2021: European Journal of Cardio-thoracic Surgery
Dong Chen, Xuanwen Bao, Ruyi Zhang, Yongfeng Ding, Min Zhang, Benfeng Li, Hangyu Zhang, Xiaolin Li, Zhou Tong, Lulu Liu, Xiaohu Zhou, Saisai Wang, Xiaofei Cheng, Yi Zheng, Jian Ruan, Weijia Fang, Peng Zhao
BACKGROUND: Colorectal neuroendocrine carcinomas (CRNECs) are highly aggressive tumours with poor prognosis and low incidence. To date, the genomic landscape and molecular pathway alterations have not been elucidated. METHODS: Tissue sections and clinical information of CRNEC (n = 35) and CR neuroendocrine tumours (CRNETs) (n = 25) were collected as an in-house cohort (2010-2020). Comprehensive genomic and expression panels (AmoyDx® Master Panel) were applied to identify the genomic and genetic alterations of CRNEC...
July 30, 2021: British Journal of Cancer
Emily Kang, Cigall Kadoch, James L Rubenstein, Lewis L Lanier, James A Wells
Therapies that boost the antitumor immune response have shown a great deal of success. Although most of these therapies have focused on enhancing T cell functions, there is a growing interest in developing therapies that can target other immune cell subsets. Like T cells, natural killer (NK) cells are cytotoxic effector cells that play a key role in the antitumor response. To advance the development of NK-based therapies, we developed a functional screen to rapidly identify antibodies that can activate NK cells...
August 3, 2021: Proceedings of the National Academy of Sciences of the United States of America
Shu-Chin Alicia Lai, Harika Gundlapalli, H Atakan Ekiz, Amanda Jiang, Elvelyn Fernandez, Alana L Welm
Immunotherapy has potential to prevent and treat metastatic breast cancer, but strategies to enhance immune-mediated killing of metastatic tumors are urgently needed. We report that a ligand-independent isoform of Ron kinase (SF-Ron) is a key target to enhance immune infiltration and eradicate metastatic tumors. Host-specific deletion of SF-Ron caused recruitment of lymphocytes to micro-metastases, augmented tumor-specific T cell responses, and nearly eliminated breast cancer metastasis in mice. Lack of host SF-Ron caused stem-like TCF1+ CD4+ T cells with type I differentiation potential to accumulate in metastases and prevent metastatic outgrowth...
July 30, 2021: Cancer Discovery
Varun Monga, Benjamin J Miller, Munir Tanas, Sarag Boukhar, Bryan Allen, Carryn Anderson, Laura Stephens, Stacey Hartwig, Steven Varga, Jon Houtman, Lei Wang, Weizhou Zhang, Omar Jaber, Jon Thomason, David Kuehn, Maheen Rajput, Catherine Metz, K D Zamba, Sarah Mott, Chinemerem Abanonu, Sudershan Bhatia, Mohammed Milhem
BACKGROUND: Soft-tissue sarcomas (STS) in the extremities and trunk treated with standard-of-care preoperative external beam radiation therapy (EBRT) followed by surgical resection are associated with local and distant relapses. In preclinical studies, oncolytic virotherapy in sarcoma has demonstrated antitumor effects via direct intratumoral oncolysis and cytotoxic T-cell-mediated immune responses. Talimogene laherparepvec (TVEC) is a replication-competent, immune-enhanced, oncolytic herpes simplex virus type 1 engineered for intratumoral injection; it has been approved by the FDA for the treatment of locally advanced and metastatic melanoma...
July 2021: Journal for Immunotherapy of Cancer
Paul Sackstein, Jacob Zaemes, Chul Kim
Cytokine release syndrome (CRS) is a well-described immune-related adverse event following chimeric antigen receptor T-cell therapy, but has rarely been reported following anti-programmed death ligand-1 therapy. We report the case of a 55-year-old man with metastatic lung adenocarcinoma who presented with fever, chills and hypotension. Initial labs were notable for highly elevated serum ferritin levels and mildly elevated triglyceride levels. He was ultimately diagnosed with pembrolizumab-induced CRS complicated by multiorgan failure...
July 2021: Journal for Immunotherapy of Cancer
Hiroyoshi Nishikawa, Shohei Koyama
With the broad application of cancer immunotherapies such as immune checkpoint inhibitors in multiple cancer types, the immunological landscape in the tumor microenvironment (TME) has become enormously important for determining the optimal cancer treatment. Tumors can be immunologically divided into two categories: inflamed and non-inflamed based on the extent of immune cell infiltration and their activation status. In general, immunotherapies are preferable for the inflamed tumors than for non-inflamed tumors...
July 2021: Journal for Immunotherapy of Cancer
Gi-Hoon Nam, Minsu Kwon, Hanul Jung, Eunbyeol Ko, Seong A Kim, Yoonjeong Choi, Su Jeong Song, Seohyun Kim, Yeji Lee, Gi Beom Kim, Jihoon Han, Jiwan Woo, Yakdol Cho, Cherlhyun Jeong, Seung-Yoon Park, Thomas M Roberts, Yong Beom Cho, In-San Kim
BACKGROUND: Statins preferentially promote tumor-specific apoptosis by depleting isoprenoid such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate. However, statins have not yet been approved for clinical cancer treatment due, in part, to poor understanding of molecular determinants on statin sensitivity. Here, we investigated the potential of statins to elicit enhanced immunogenicity of KRAS -mutant ( KRAS mut ) tumors. METHODS: The immunogenicity of treated cancer cells was determined by western blot, flow cytometry and confocal microscopy...
July 2021: Journal for Immunotherapy of Cancer
Özcan Çınar, Bernadette Brzezicha, Corinna Grunert, Peter Michael Kloetzel, Christin Beier, Caroline Anna Peuker, Ulrich Keller, Antonio Pezzutto, Antonia Busse
BACKGROUND: Adoptive transfer of engineered T cells has shown remarkable success in B-cell malignancies. However, the most common strategy of targeting lineage-specific antigens can lead to undesirable side effects. Also, a substantial fraction of patients have refractory disease. Novel treatment approaches with more precise targeting may be an appealing alternative. Oncogenic somatic mutations represent ideal targets because of tumor specificity. Mutation-derived neoantigens can be recognized by T-cell receptors (TCRs) in the context of MHC-peptide presentation...
July 2021: Journal for Immunotherapy of Cancer
Sigrid Dubois, Thomas A Waldmann, Jürgen R Müller
T cell lymphomas arise in mice that constitutively express a single TCR in the absence of NK cells. Upon TCR engagement these lymphomas are able to corrupt tumor surveillance by decreasing NK cell numbers. In this study, we investigate the outcome of interactions between these T cell lymphomas and dendritic cells. Bone marrow-derived dendritic cells mediated effective killing of T cell lymphomas after activation with IFN-γ and TLR ligands in culture. This cytotoxicity was independent of MHC compatibility. Cell lysis was reduced by the presence of the peroxynitrite inhibitors FeTTPS and L-NMMA, whereas inhibitors of apoptosis, death receptors, and degranulation were without effect, suggesting NO metabolites as the main mediators...
July 30, 2021: Journal of Immunology
Á Pinto, M Álvarez-Maestro
No abstract text is available yet for this article.
July 27, 2021: Actas Urologicas Españolas
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