keyword
https://read.qxmd.com/read/38298193/refining-patient-selection-for-next-generation-immunotherapeutic-early-phase-clinical-trials-with-a-novel-and-externally-validated-prognostic-nomogram
#21
JOURNAL ARTICLE
Agnese Losurdo, Angelo Dipasquale, Laura Giordano, Pasquale Persico, Elena Lorenzi, Antonio Di Muzio, Chiara Barigazzi, James Korolewicz, Aman Mehan, Oreoluwa Mohammed, Benhard Scheiner, David J Pinato, Armando Santoro, Matteo Simonelli
INTRODUCTION: Identifying which patient may benefit from immunotherapeutic early-phase clinical trials is an unmet need in drug development. Among several proposed prognostic scores, none has been validated in patients receiving immunomodulating agents (IMAs)-based combinations. PATIENTS AND METHODS: We retrospectively collected data of 208 patients enrolled in early-phase clinical trials investigating IMAs at our Institution, correlating clinical and blood-based variables with overall survival (OS)...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38288307/glioblastoma-with-high-o6-methyl-guanine-dna-methyltransferase-expression-are-more-immunologically-active-than-tumors-with-low-mgmt-expression
#22
JOURNAL ARTICLE
Yoshihiro Kushihara, Shota Tanaka, Yukari Kobayashi, Koji Nagaoka, Miyu Kikuchi, Takahide Nejo, Erika Yamazawa, Shohei Nambu, Kazuha Kugasawa, Hirokazu Takami, Shunsaku Takayanagi, Nobuhito Saito, Kazuhiro Kakimi
BACKGROUND: Glioblastoma (GBM) is a highly lethal brain tumor. The effectiveness of temozolomide (TMZ) treatment in GBM is linked to the methylation status of O6-methyl-guanine DNA methyltransferase ( MGMT ) promoter. Patients with unmethylated MGMT promoter have limited treatment options available. Consequently, there is a pressing need for alternative therapeutic strategies for such patients. METHODS: Data, including transcriptomic and clinical information, as well as information on MGMT promoter methylation status in primary GBM, were obtained from The Cancer Genome Atlas (TCGA) (n=121) and Chinese Glioma Genome Atlas (CGGA) (n=83) datasets...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38278031/signaling-pathways-underlying-tgf-%C3%AE-mediated-suppression-of-il-12a-gene-expression-in-monocytes
#23
JOURNAL ARTICLE
Tetiana Hourani, Mahtab Eivazitork, Thivya Balendran, Kevin Mc Lee, John A Hamilton, Hong-Jian Zhu, Josephine Iaria, Andrew P Morokoff, Rodney B Luwor, Adrian A Achuthan
Transforming growth factor-β (TGF-β) is a pleiotropic cytokine essential for multiple biological processes, including the regulation of inflammatory and immune responses. One of the important functions of TGF-β is the suppression of the proinflammatory cytokine interleukin-12 (IL-12), which is crucial for mounting an anti-tumorigenic response. Although the regulation of the IL-12p40 subunit (encoded by the IL-12B gene) of IL-12 has been extensively investigated, the knowledge of IL-12p35 (encoded by IL-12A gene) subunit regulation is relatively limited...
January 25, 2024: Molecular Immunology
https://read.qxmd.com/read/38268001/mrna-based-precision-targeting-of-neoantigens-and-tumor-associated-antigens-in-malignant-brain-tumors
#24
JOURNAL ARTICLE
Vrunda Trivedi, Changlin Yang, Kelena Klippel, Oleg Yegorov, Christina von Roemeling, Lan Hoang-Minh, Graeme Fenton, Elizabeth Ogando-Rivas, Paul Castillo, Ginger Moore, Kaytora Long-James, Kyle Dyson, Bently Doonan, Catherine Flores, Duane A Mitchell
BACKGROUND: Despite advancements in the successful use of immunotherapy in treating a variety of solid tumors, applications in treating brain tumors have lagged considerably. This is due, at least in part, to the lack of well-characterized antigens expressed within brain tumors that can mediate tumor rejection; the low mutational burden of these tumors that limits the abundance of targetable neoantigens; and the immunologically "cold" tumor microenvironment that hampers the generation of sustained and productive immunologic responses...
January 25, 2024: Genome Medicine
https://read.qxmd.com/read/38263486/phase-i-study-targeting-newly-diagnosed-grade-4-astrocytoma-with-bispecific-antibody-armed-t-cells-egfr-bats-in-combination-with-radiation-and-temozolomide
#25
JOURNAL ARTICLE
Camilo E Fadul, Archana Thakur, Jungeun Kim, Jessica Kassay-McAllister, Dana Schalk, M Beatriz Lopes, Joseph Donahue, Benjamin Purow, Patrick Dillon, Tri Le, David Schiff, Qin Liu, Lawrence G Lum
PURPOSE: The purpose of this study was to determine the safety, feasibility, and immunologic responses of treating grade 4 astrocytomas with multiple infusions of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed T cells (EGFR BATs) in combination with radiation and chemotherapy. METHODS: This phase I study used a 3 + 3 dose escalation design to test the safety and feasibility of intravenously infused EGFR BATs in combination with radiation and temozolomide (TMZ) in patients with newly diagnosed grade 4 astrocytomas (AG4)...
January 23, 2024: Journal of Neuro-oncology
https://read.qxmd.com/read/38261253/hcmv-ie1-ie1mut-therapeutic-vaccine-induces-tumor-regression-via-intratumoral-tertiary-lymphoid-structure-formation-and-peripheral-immunity-activation-in-glioblastoma-multiforme
#26
JOURNAL ARTICLE
Xiaoli Yang, Shasha Jiang, Fengjun Liu, Zonghui Li, Wenxuan Liu, Xianjuan Zhang, Fulong Nan, Jun Li, Meng Yu, Yunyang Wang, Bin Wang
Glioblastoma multiforme (GBM), a highly malignant invasive brain tumor, is associated with poor prognosis and survival and lacks an effective cure. High expression of the human cytomegalovirus (HCMV) immediate early protein 1 (IE1) in GBM tissues is strongly associated with their malignant progression, presenting a novel target for therapeutic strategies. Here, the bioluminescence imaging technology revealed remarkable tumor shrinkage and improved survival rates in a mouse glioma model treated with HCMV IE1/IE1mut vaccine...
January 23, 2024: Molecular Neurobiology
https://read.qxmd.com/read/38247970/biophysical-control-of-the-glioblastoma-immunosuppressive-microenvironment-opportunities-for-immunotherapy
#27
REVIEW
Landon Teer, Kavitha Yaddanapudi, Joseph Chen
GBM is the most aggressive and common form of primary brain cancer with a dismal prognosis. Current GBM treatments have not improved patient survival, due to the propensity for tumor cell adaptation and immune evasion, leading to a persistent progression of the disease. In recent years, the tumor microenvironment (TME) has been identified as a critical regulator of these pro-tumorigenic changes, providing a complex array of biomolecular and biophysical signals that facilitate evasion strategies by modulating tumor cells, stromal cells, and immune populations...
January 18, 2024: Bioengineering
https://read.qxmd.com/read/38203185/comparative-insight-into-microglia-macrophages-associated-pathways-in-glioblastoma-and-alzheimer-s-disease
#28
REVIEW
Jian Shi, Shiwei Huang
Microglia and macrophages are pivotal to the brain's innate immune response and have garnered considerable attention in the context of glioblastoma (GBM) and Alzheimer's disease (AD) research. This review delineates the complex roles of these cells within the neuropathological landscape, focusing on a range of signaling pathways-namely, NF-κB, microRNAs (miRNAs), and TREM2-that regulate the behavior of tumor-associated macrophages (TAMs) in GBM and disease-associated microglia (DAMs) in AD. These pathways are critical to the processes of neuroinflammation, angiogenesis, and apoptosis, which are hallmarks of GBM and AD...
December 19, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/38201248/the-biological-and-clinical-role-of-the-telomerase-reverse-transcriptase-gene-in-glioblastoma-a-potential-therapeutic-target
#29
REVIEW
Vincenzo Di Nunno, Marta Aprile, Stefania Bartolini, Lidia Gatto, Alicia Tosoni, Lucia Ranieri, Dario De Biase, Sofia Asioli, Enrico Franceschi
Glioblastoma IDH -wildtype represents the most lethal and frequent primary tumor of the central nervous system. Thanks to important scientific efforts, we can now investigate its deep genomic assessment, elucidating mutated genes and altered biological mechanisms in addition to its clinical aggressiveness. The telomerase reverse transcriptase gene ( TERT ) is the most frequently altered gene in solid tumors, including brain tumors and GBM IDH -wildtype. In particular, it can be observed in approximately 80-90% of GBM IDH -wildtype cases...
December 25, 2023: Cells
https://read.qxmd.com/read/38171932/mrgps-an-m6a-related-gene-pair-signature-to-predict-the-prognosis-and-immunological-impact-of-glioma-patients
#30
JOURNAL ARTICLE
Ning Zhang, Fengxia Yang, Pengfei Zhao, Nana Jin, Haonan Wu, Tao Liu, Qingshan Geng, Xiaojun Yang, Lixin Cheng
N6-methyladenosine (m6A) RNA methylation is the predominant epigenetic modification for mRNAs that regulates various cancer-related pathways. However, the prognostic significance of m6A modification regulators remains unclear in glioma. By integrating the TCGA lower-grade glioma (LGG) and glioblastoma multiforme (GBM) gene expression data, we demonstrated that both the m6A regulators and m6A-target genes were associated with glioma prognosis and activated various cancer-related pathways. Then, we paired m6A regulators and their target genes as m6A-related gene pairs (MGPs) using the iPAGE algorithm, among which 122 MGPs were significantly reversed in expression between LGG and GBM...
November 22, 2023: Briefings in Bioinformatics
https://read.qxmd.com/read/38161192/immunostimulatory-nanoparticles-delivering-cytokines-as-a-novel-cancer-nanoadjuvant-to-empower-glioblastoma-immunotherapy
#31
JOURNAL ARTICLE
Flávia Sousa, Henry Lee, Mauro Almeida, Amelie Bazzoni, Barbara Rothen-Rutishauser, Alke Petri-Fink
Glioblastoma (GBM) stands as a highly aggressive and deadly malignant primary brain tumor with a median survival time of under 15 months upon disease diagnosis. While immunotherapies have shown promising results in solid cancers, brain cancers are still unresponsive to immunotherapy due to immunological dysfunction and the presence of a blood-brain barrier. Interleukin-12 (IL-12) emerges as a potent cytokine in fostering anti-tumor immunity by triggering interferon-gamma production in T and natural killer cells and changing macrophages to a tumoricidal phenotype...
December 31, 2023: Drug Delivery and Translational Research
https://read.qxmd.com/read/38134933/time-resolved-single-cell-transcriptomics-defines-immune-trajectories-in-glioblastoma
#32
JOURNAL ARTICLE
Daniel Kirschenbaum, Ken Xie, Florian Ingelfinger, Yonatan Katzenelenbogen, Kathleen Abadie, Thomas Look, Fadi Sheban, Truong San Phan, Baoguo Li, Pascale Zwicky, Ido Yofe, Eyal David, Kfir Mazuz, Jinchao Hou, Yun Chen, Hila Shaim, Mayra Shanley, Soeren Becker, Jiawen Qian, Marco Colonna, Florent Ginhoux, Katayoun Rezvani, Fabian J Theis, Nir Yosef, Tobias Weiss, Assaf Weiner, Ido Amit
Deciphering the cell-state transitions underlying immune adaptation across time is fundamental for advancing biology. Empirical in vivo genomic technologies that capture cellular dynamics are currently lacking. We present Zman-seq, a single-cell technology recording transcriptomic dynamics across time by introducing time stamps into circulating immune cells, tracking them in tissues for days. Applying Zman-seq resolved cell-state and molecular trajectories of the dysfunctional immune microenvironment in glioblastoma...
January 4, 2024: Cell
https://read.qxmd.com/read/38130720/ros-regulation-in-gliomas-implications-for-treatment-strategies
#33
REVIEW
Yu-Chen Yang, Yu Zhu, Si-Jia Sun, Can-Jun Zhao, Yang Bai, Jin Wang, Li-Tian Ma
Gliomas are one of the most common primary malignant tumours of the central nervous system (CNS), of which glioblastomas (GBMs) are the most common and destructive type. The glioma tumour microenvironment (TME) has unique characteristics, such as hypoxia, the blood-brain barrier (BBB), reactive oxygen species (ROS) and tumour neovascularization. Therefore, the traditional treatment effect is limited. As cellular oxidative metabolites, ROS not only promote the occurrence and development of gliomas but also affect immune cells in the immune microenvironment...
2023: Frontiers in Immunology
https://read.qxmd.com/read/38107534/the-regression-of-glioblastoma-multiforme-is-time-dependent-in-the-wild-type-rat-xenograft-model
#34
JOURNAL ARTICLE
Seyed Noureddin Nematollahi-Mahani, Sepideh Ganjalikhan-Hakemi, Zahra Abdi
INTRODUCTION: Glioblastoma multiforme (GBM) is an aggressive case of primary brain cancer which remains among the most fatal tumors worldwide. Although, some in vitro and in vivo models have been developed for a better understanding of GBM behavior; a natural model of GBM would improve the efficiency of experimental models of human GBM tumors. We aimed the present study to examine the survival and durability of U87 cells in the brain of wild-type rats. METHODS: U87 cells were intracranially implanted in twenty-one wild-type rats...
2023: Basic and Clinical Neuroscience
https://read.qxmd.com/read/38102349/immunological-sex-differences-in-glioblastoma
#35
JOURNAL ARTICLE
Felicity Tournant
No abstract text is available yet for this article.
December 15, 2023: Nature Cancer
https://read.qxmd.com/read/38091354/single-cell-transcriptomics-reveals-the-heterogeneity-of-the-immune-landscape-of-idh-wildtype-high-grade-gliomas
#36
JOURNAL ARTICLE
Xiaojuan Ran, Jian Zheng, Lingchao Chen, Zhen Xia, Yin Wang, Chengfang Sun, Chen Guo, Peng Lin, Fuyi Liu, Chun Wang, Jianguo Zhou, Chongran Sun, Qichang Liu, Jianzhu Ma, Zhiyong Qin, Xiangdong Zhu, Qi Xie
Isocitrate dehydrogenase (IDH)-wildtype (WT) high-grade gliomas, especially glioblastomas, are highly aggressive and have an immunosuppressive tumor microenvironment. Although tumor-infiltrating immune cells are known to play a critical role in glioma genesis, their heterogeneity and intercellular interactions remain poorly understood. In this study, we constructed a single-cell transcriptome landscape of immune cells from tumor tissue and matching peripheral blood mononuclear cells (PBMCs) from IDH-WT high-grade glioma patients...
December 13, 2023: Cancer Immunology Research
https://read.qxmd.com/read/38085056/neuroblastoma-and-glioblastoma-cases-with-amplified-oncogenes-have-reduced-numbers-of-tumor-resident-adaptive-immune-receptor-recombinations
#37
JOURNAL ARTICLE
Toriana R Dabkowski, Mallika Varkhedi, Joanna J Song, Etienne C Gozlan, George Blanck
PURPOSE: In certain cancers, oncogene amplification is correlated with an immunologically cold or noninflamed, tumor immune microenvironment (TIME) and a worse prognosis, for example, in the case of MYCN-amplified neuroblastoma (NBL). However, for other cancer types, the relationship between oncogene amplification and immune response is more complicated or unresolved. One such cancer is glioblastoma multiforme (GBM), in which the epidermal growth factor receptor (EGFR) oncogene is commonly amplified...
September 2023: JCO Precision Oncology
https://read.qxmd.com/read/38071912/predictive-role-of-e2f6-in-cancer-prognosis-and-responses-of-immunotherapy
#38
JOURNAL ARTICLE
Chuandong Gong, Zewei Tu, Xiaoyan Long, Xinjun Liu, Feng Liu, Jia Liu, Xingen Zhu, Jingying Li, Kai Huang
BACKGROUND: E2F6 is a member of the E2F transcription factor family. Numerous studies have demonstrated that E2F6 is critical to cancer development and progression, but its role in cancer immunotherapy remains unclear. METHODS: Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases were used to obtain RNA-seq data for cancer and normal tissues, and we utilized the cBioPortal to analyze E2F6 genomic alterations in pan-cancer. The protein localization of E2F6 was obtained using the Human Protein Atlas (HPA), and the upregulation of E2F6 expression in clinical glioblastoma multiforme (GBM) tissues was detected by Western blot analysis...
December 9, 2023: International Immunopharmacology
https://read.qxmd.com/read/38053639/tigit-contributes-to-the-regulation-of-4-1bb-and-does-not-define-nk-cell-dysfunction-in-glioblastoma
#39
JOURNAL ARTICLE
Kyle B Lupo, Sandra Torregrosa-Allen, Bennett D Elzey, Sagar Utturkar, Nadia A Lanman, Aaron A Cohen-Gadol, Veronika Slivova, MacKenzie McIntosh, Karen E Pollok, Sandro Matosevic
TIGIT is a receptor on human natural killer (NK) cells. Here, we report that TIGIT does not spontaneously induce inhibition of NK cells in glioblastoma (GBM), but rather acts as a decoy-like receptor, by usurping binding partners and regulating expression of NK activating ligands and receptors. Our data show that in GBM patients, one of the underpinnings of unresponsiveness to TIGIT blockade is that by targeting TIGIT, NK cells do not lose an inhibitory signal, but gains the potential for new interactions with other, shared, TIGIT ligands...
December 15, 2023: IScience
https://read.qxmd.com/read/38022656/comparison-of-peripheral-leukocyte-parameters-in-patients-receiving-conventionally-and-hypofractionated-radiotherapy-schemes-for-the-treatment-of-newly-diagnosed-glioblastoma
#40
JOURNAL ARTICLE
Lindsey Greenlund, Ryan Shanley, Kellen Mulford, Elizabeth C Neil, Jessica Lawrence, Susan Arnold, Michael Olin, G Elizabeth Pluhar, Andrew S Venteicher, Clark C Chen, Clara Ferreira, Margaret Reynolds, L Chinsoo Cho, Christopher Wilke, B Aika Shoo, Jianling Yuan, Kathryn Dusenbery, Lawrence R Kleinberg, Stephanie A Terezakis, Lindsey Sloan
INTRODUCTION: Treatment for glioblastomas, aggressive and nearly uniformly fatal brain tumors, provide limited long-term success. Immunosuppression by myeloid cells in both the tumor microenvironment and systemic circulation are believed to contribute to this treatment resistance. Standard multi-modality therapy includes conventionally fractionated radiotherapy over 6 weeks; however, hypofractionated radiotherapy over 3 weeks or less may be appropriate for older patients or populations with poor performance status...
2023: Frontiers in Immunology
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