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JOURNAL ARTICLE
Alessandra De Leo, Alessio Ugolini, Xiaoqing Yu, Fabio Scirocchi, Delia Scocozza, Barbara Peixoto, Angelica Pace, Luca D'Angelo, James K C Liu, Arnold B Etame, Aurelia Rughetti, Marianna Nuti, Antonio Santoro, Michael A Vogelbaum, Jose R Conejo-Garcia, Paulo C Rodriguez, Filippo Veglia
Immunosuppressive macrophages restrict anti-cancer immunity in glioblastoma (GBM). Here, we studied the contribution of microglia (MGs) and monocyte-derived macrophages (MDMs) to immunosuppression and mechanisms underlying their regulatory function. MDMs outnumbered MGs at late tumor stages and suppressed T cell activity. Molecular and functional analysis identified a population of glycolytic MDM expressing GLUT1 with potent immunosuppressive activity. GBM-derived factors promoted high glycolysis, lactate, and interleukin-10 (IL-10) production in MDMs...
April 30, 2024: Immunity
#22
JOURNAL ARTICLE
Irina Veith, Martin Nurmik, Arianna Mencattini, Isabelle Damei, Christine Lansche, Solenn Brosseau, Giacomo Gropplero, Stéphanie Corgnac, Joanna Filippi, Nicolas Poté, Edouard Guenzi, Anaïs Chassac, Pierre Mordant, Jimena Tosello, Christine Sedlik, Eliane Piaggio, Nicolas Girard, Jacques Camonis, Hamasseh Shirvani, Fathia Mami-Chouaib, Fatima Mechta-Grigoriou, Stéphanie Descroix, Eugenio Martinelli, Gérard Zalcman, Maria Carla Parrini
There is a compelling need for approaches to predict the efficacy of immunotherapy drugs. Tumor-on-chip technology exploits microfluidics to generate 3D cell co-cultures embedded in hydrogels that recapitulate simplified tumor ecosystems. Here, we present the development and validation of lung tumor-on-chip platforms to quickly and precisely measure ex vivo the effects of immune checkpoint inhibitors on T cell-mediated cancer cell death by exploiting the power of live imaging and advanced image analysis algorithms...
April 27, 2024: Cell reports medicine
#23
JOURNAL ARTICLE
Ginny Xiaohe Li, Lijun Chen, Yi Hsiao, Rahul Mannan, Yuping Zhang, Jie Luo, Francesca Petralia, Hanbyul Cho, Noshad Hosseini, Felipe da Veiga Leprevost, Anna Calinawan, Yize Li, Shankara Anand, Aniket Dagar, Yifat Geffen, Chandan Kumar-Sinha, Seema Chugh, Anne Le, Sean Ponce, Shenghao Guo, Cissy Zhang, Michael Schnaubelt, Nataly Naser Al Deen, Feng Chen, Wagma Caravan, Andrew Houston, Alex Hopkins, Chelsea J Newton, Xiaoming Wang, Daniel A Polasky, Sarah Haynes, Fengchao Yu, Xiaojun Jing, Siqi Chen, Ana I Robles, Mehdi Mesri, Mathangi Thiagarajan, Eunkyung An, Gad A Getz, W Marston Linehan, Galen Hostetter, Scott D Jewell, Daniel W Chan, Pei Wang, Gilbert S Omenn, Rohit Mehra, Christopher J Ricketts, Li Ding, Arul M Chinnaiyan, Marcin P Cieslik, Saravana M Dhanasekaran, Hui Zhang, Alexey I Nesvizhskii
Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes. RCCs with high genome instability display overexpression of IGF2BP3 and PYCR1...
April 26, 2024: Cell reports medicine
#24
JOURNAL ARTICLE
High serum sodium predicts immunotherapy response in metastatic renal cell and urothelial carcinoma.
Niklas Klümper, Alexander Cox, Markus Eckstein, Christoph Kuppe, Manuel Ritter, Peter Brossart, Julian Luetkens, Michael Hölzel, Johannes Stein, Jonas Saal
OBJECTIVES: The development of reliable biomarkers for the prediction of immune checkpoint inhibition (ICI) response in patients with metastatic renal cell carcinoma (mRCC) and urothelial carcinoma (mUC) remains an unresolved challenge. Conventional ICI biomarkers typically focus on tumor-related factors such as PD-L1 expression. However, a comprehensive evaluation of the predictive value of serum electrolyte levels, a so far widely unexplored area, is still pending. METHODS: We conducted a post-hoc analysis of baseline sodium, potassium, chloride, magnesium and calcium levels in two independent phase 3 clinical trials: IMvigor211 for mUC comparing atezolizumab to chemotherapy, and IMmotion151 for mRCC comparing atezolizumab+bevacizumab to sunitinib...
April 28, 2024: European Journal of Cancer
#25
REVIEW
Umair Mahmood, Ewa Carrier, Khurum Khan
Traditional chemotherapy-based adjuvant therapies for locally advanced pancreatic ductal adenocarcinoma (PDAC) have been associated with poor clinical outcomes driven partly by its complex anatomy and molecular heterogeneity. Treatment for PDAC is challenged by presence of a dense tumour microenvironment involving an interplay of multiple tumoural and stromal components which promote metastatic oncogenic behaviour. PDAC also involves aberrations in multiple signalling pathways with paucity of treatment options against the most common mutations including KRAS, TP53, CDKN2A andSMAD4...
May 3, 2024: Cancer Treatment Reviews
#26
REVIEW
Nan Zhong, Qihong Ma, Shiting Gong, Yuanyuan Shi, Lijun Zhao, Danyu Wang, Huanhuan Zhou, Ning Liu, Yuan Ye, Jianxun Wang, Liqiong Liu, Zhi Guo
CD19-directed chimeric antigen receptor (CAR) T cell therapy has been shown to achieve a considerably durable response in patients with refractory or relapsed B cell non-Hodgkin lymphomas. Most of these CARs were generated by lentivirus. With the exception of Yescarta and Tecartus, few patients with relapsed-/refractory- lymphoma have been treated clinically with a CARs using retroviral vector (RV). Here, we reported a relapsed/refractory grade 2 follicular lymphoma patient with multiple chemotherapy failures, and was treated with a novel CD19 CAR-T cell manufactured from a RV...
May 3, 2024: International Immunopharmacology
#27
JOURNAL ARTICLE
Yue Wang, Yinyin Cao, Yang Li, Fenhua Zhu, Meifen Yuan, Jin Xu, Xiaojing Ma, Jian Li
BACKGROUND: Approximately 10-20% of Kawasaki disease (KD) patients suffer from intravenous immunoglobulin (IVIG) resistance, placing them at higher risk of developing coronary artery aneurysms. Therefore, we aimed to construct an IVIG resistance prediction tool for children with KD in Shanghai, China. METHODS: Retrospective analysis was conducted on data from 1271 patients diagnosed with KD and the patients were randomly divided into a training set and a validation set in a 2:1 ratio...
May 3, 2024: International Immunopharmacology
#28
JOURNAL ARTICLE
Yongfu Lou, Zonghao Li, Han Zheng, Zhongze Yuan, Wenxiang Li, Jianping Zhang, Wenyuan Shen, Yiming Gao, Ning Ran, Xiaohong Kong, Shiqing Feng
Spinal cord injury (SCI) is a devastating condition for which effective clinical treatment is currently lacking. During the acute phase of SCI, myriad pathological changes give rise to subsequent secondary injury. The results of our previous studies indicated that treating rats post-SCI with nafamostat mesilate (NM) protected the blood-spinal cord barrier (BSCB) and exerted an antiapoptotic effect. However, the optimal dosage for mice with SCI and the underlying mechanisms potentially contributing to recovery, especially during the acute phase of SCI, have not been determined...
May 3, 2024: International Immunopharmacology
#29
JOURNAL ARTICLE
Dongfen Guo, Lele Hu, Peng Xie, Ping Sun, Wenfeng Yu
Seipin plays a crucial role in lipid metabolism and is involved in neurological disorders. However, the function and mechanism of action of seipin in acute ischemic stroke have not yet been elucidated. Here, we aimed to investigate the effect of seipin on neuroinflammation induced by oxygen-glucose deprivation/reoxygenation (OGD/R) and further explore the molecular mechanism by functional experiments. Our results revealed a significant decrease in seipin mRNA levels, accompanied by enhanced expression of TNF-α in patients with AIS, and a significant negative correlation between seipin and TNF-α was observed...
May 3, 2024: International Immunopharmacology
#30
JOURNAL ARTICLE
Tohid Piri-Gharaghie, Ghazal Ghajari, Golnoosh Rezaeizadeh, Mohaned Adil, Mohammed H Mahdi
Brucella infections typically occur in mucosal membranes, emphasizing the need for mucosal vaccinations. This study evaluated the effectiveness of orally administering Lactococcus lactis (L. lactis) for producing the Brucella abortus multi-epitope OMPs peptide. A multi-epitope plasmid was generated through a reverse vaccinology method, and mice were administered the genetically modified L. lactis orally as a vaccine. The plasmid underwent digestion, synthesizing a 39 kDa-sized protein known as OMPs by the target group...
May 3, 2024: International Immunopharmacology
#31
JOURNAL ARTICLE
Wenjie Zhu, Shimin Zhao, Xiufeng Cheng, Changlei Wu, Zitao Liu, Jun Huang
BACKGROUND: The clinical significance and comprehensive characteristics of chemokines and chemokine receptors in colorectal cancer (CRC) have not been previously reported. Our study aims to investigate the expression profiles of chemokines and chemokine receptors, as well as establish subtypes in CRC. METHODS: 1009 CRC samples were enrolled in our study. Consensus unsupervised clustering analysis was conducted to establish subtypes, and a risk score model was developed using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses...
May 3, 2024: International Immunopharmacology
#32
JOURNAL ARTICLE
Xiaorui Ding, Huarui Liu, Qinghua Xu, Tong Ji, Ranxun Chen, Zhengcheng Liu, Jinghong Dai
BACKGROUND: Epidemiological evidence has indicated the occurrence of idiopathic pulmonary fibrosis (IPF) with coexisting lung cancer is not a coincidence. The pathogenic mechanisms shared between IPF and non-small cell lung cancer (NSCLC) at the transcriptional level remain elusive and need to be further elucidated. METHODS: IPF and NSCLC datasets of expression profiles were obtained from the GEO database. Firstly, to detect the shared dysregulated genes positively correlated with both IPF and NSCLC, differentially expressed analysis and WGCNA analysis were carried out...
May 3, 2024: International Immunopharmacology
#33
REVIEW
Shiv Bharadwaj, Yaroslava Groza, Joanna M Mierzwicka, Petr Malý
Triggering receptor expressed on myeloid cells 2 (TREM-2), a glycosylated receptor belonging to the immunoglobin superfamily and especially expressed in the myeloid cell lineage, is frequently explained as a reminiscent receptor for both adaptive and innate immunity regulation. TREM-2 is also acknowledged to influence NK cell differentiation via the PI3K and PLCγ signaling pathways, as well as the partial activation or direct inhibition of T cells. Additionally, TREM-2 overexpression is substantially linked to cell-specific functions, such as enhanced phagocytosis, reduced toll-like receptor (TLR)-mediated inflammatory cytokine production, increased transcription of anti-inflammatory cytokines, and reshaped T cell function...
May 3, 2024: International Immunopharmacology
#34
REVIEW
Yu Zhang, Xiangxiang Zhou
Regulated cell death (RCD) is a form of cell death that can be regulated by numerous biomacromolecules. Accumulating evidence suggests that dysregulated expression and altered localization of related proteins in RCD promote the development of cancer. Targeting subroutines of RCD with pharmacological small-molecule compounds is becoming a promising therapeutic avenue for anti-tumor treatment, especially in hematological malignancies. Herein, we summarize the aberrant mechanisms of apoptosis, necroptosis, pyroptosis, PANoptosis, and ferroptosis in hematological malignancies...
May 3, 2024: Biomedicine & Pharmacotherapy
#35
JOURNAL ARTICLE
L Buisseret, Y Bareche, D Venet, E Girard, A Gombos, P Emonts, S Majjaj, G Rouas, M Serra, V Debien, E Agostinetto, S Garaud, K Willard-Gallo, D Larsimont, J Stagg, F Rothé, C Sotiriou
BACKGROUND: Immune checkpoint blockade (ICB) in combination with chemotherapy improves outcome of patients with triple-negative breast cancer (TNBC) in metastatic and early settings. The identification of predictive biomarkers able to guide treatment decisions is challenging and currently limited to programmed death-ligand 1 (PD-L1) expression and high tumor mutational burden (TMB) in the advanced setting, with several limitations. MATERIALS AND METHODS: We carried out a retrospective analysis of clinical-pathological and molecular characteristics of tumor samples from 11 patients with advanced TNBC treated with single-agent pembrolizumab participating in two early-phase clinical trials: KEYNOTE-012 and KEYNOTE-086...
May 3, 2024: ESMO Open
#36
JOURNAL ARTICLE
Yao Fei, Danping Cao, Runyu Dong, Yanna Li, Zhixiong Wang, Peng Gao, Menglin Zhu, Xiaoming Wang, Xueliang Zuo, Juan Cai
BACKGROUND: Cuproptosis, as a unique modality of regulated cell death, requires the involvement of ubiquitin-binding enzyme UBE2D2. However, the prognostic and immunotherapeutic values of UBE2D2 in pan-cancer remain largely unknown. METHODS: Using UCSC Xena, TIMER, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) databases, we aimed to explore the differential expression pattern of UBE2D2 across multiple cancer types and to evaluate its association with patient prognosis, clinical features, and genetic variations...
May 4, 2024: Clinical & Translational Oncology
#37
REVIEW
Anchi Sun, Zhiwei Xing, Rongrong Lv, Pengyuan Niu, Bao Zhao, Shiyin Ma, Hui Li
Head and neck cancer accounts for about one-fifth of all malignant tumors, and the incidence is increasing year by year. The overall mortality rate was high and the 5-year survival rate was low. At present, the combination of surgery, radiotherapy, and chemotherapy is the main treatment in clinical practice, but the treatment of recurrent or metastatic advanced head and neck cancer is still a challenge. With the rise of immunotherapy, more and more studies on immune checkpoint inhibitors have been conducted...
May 4, 2024: Medical Oncology
#38
JOURNAL ARTICLE
Yaqian Du, Xudong Zhao, Fei He, Haijiang Gong, Jiani Yang, Linzhi Wu, Xianchang Cui, Shili Gai, Piaoping Yang, Jun Lin
Low efficacy of immunotherapy due to the poor immunogenicity of most tumors and their insufficient infiltration by immune cells highlights the importance of inducing immunogenic cell death and activating immune system for achieving better treatment outcomes. Herein, ferroelectric Bi2 CuO4 nanoparticles (NPs) with rich copper vacancies (named BCO-VCu ) were rationally designed and engineered for ferroelectricity enhanced apoptosis, cuproptosis, and the subsequently evoked immunotherapy. In this structure, the suppressed recombination of the electron-hole pairs by the vacancies and the band bending by the ferroelectric polarization lead to high catalytic activiy, triggering reactive oxygen species bursts and inducing apoptosis...
May 4, 2024: Advanced Materials
#39
JOURNAL ARTICLE
Matteo Tanzi, Enrica Montini, Agnese Rumolo, Antonia Moretta, Patrizia Comoli, Gloria Acquafredda, Jessica Rotella, Gloria Taurino, Francesca Compagno, Francesco Delle Cave, Cesare Perotti, Gian Luigi Marseglia, Marco Zecca, Daniela Montagna
BACKGROUND AIMS: Somatic cell therapy based on the infusion of donor-derived cytotoxic T lymphocytes (CTL) able to recognize patients' leukemia blasts (LB) is a promising approach to control leukemia relapse after allogeneic HSCT. The success of this approach strongly depends on the ex vivo generation of high-quality donor-derived anti-leukemia CTL in compliance with Good Manufacturing Practices (GMP). We previously described a procedure for generating large numbers of donor-derived anti-leukemia CTL through stimulation of CD8-enriched lymphocytes with dendritic cells (DCs) pulsed with apoptotic LB in the presence of interleukin (IL)-12, IL-7 and IL-15...
April 20, 2024: Cytotherapy
#40
REVIEW
Baishali Tamuli, Sakshi Sharma, Meena Patkar, Subir Biswas
BACKGROUND: The tumor microenvironment of solid tumors governs the differentiation of otherwise non-immunosuppressive macrophages and gamma delta (γδ) T cells into strong immunosuppressors while promoting suppressive abilities of known immunosuppressors such as myeloid-derived suppressor cells (MDSCs) upon infiltration into the tumor beds. RECENT FINDINGS: In epithelial malignancies, tumor-associated macrophages (TAMs), precursor monocytic MDSCs (M-MDSCs), and gamma delta (γδ) T cells often acquire strong immunosuppressive abilities that dampen spontaneous immune responses by tumor-infiltrating T cells and B lymphocytes against cancer...
May 2024: Cancer reports
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