keyword
https://read.qxmd.com/read/38536921/glutamine-antagonist-drp-104-suppresses-tumor-growth-and-enhances-response-to-checkpoint-blockade-in-keap1-mutant-lung-cancer
#1
JOURNAL ARTICLE
Ray Pillai, Sarah E LeBoeuf, Yuan Hao, Connie New, Jenna L E Blum, Ali Rashidfarrokhi, Shih Ming Huang, Christian Bahamon, Warren L Wu, Burcu Karadal-Ferrena, Alberto Herrera, Ellie Ivanova, Michael Cross, Jozef P Bossowski, Hongyu Ding, Makiko Hayashi, Sahith Rajalingam, Triantafyllia Karakousi, Volkan I Sayin, Kamal M Khanna, Kwok-Kin Wong, Robert Wild, Aristotelis Tsirigos, John T Poirier, Charles M Rudin, Shawn M Davidson, Sergei B Koralov, Thales Papagiannakopoulos
Loss-of-function mutations in KEAP1 frequently occur in lung cancer and are associated with poor prognosis and resistance to standard of care treatment, highlighting the need for the development of targeted therapies. We previously showed that KEAP1 mutant tumors consume glutamine to support the metabolic rewiring associated with NRF2-dependent antioxidant production. Here, using preclinical patient-derived xenograft models and antigenic orthotopic lung cancer models, we show that the glutamine antagonist prodrug DRP-104 impairs the growth of KEAP1 mutant tumors...
March 29, 2024: Science Advances
https://read.qxmd.com/read/38524742/effectiveness-of-pd1-pd-l1-combined-with-anti-angiogenic-drugs-in-patients-with-advanced-nonsmall-cell-lung-cancer-a-systematic-review-and-meta-analysis
#2
REVIEW
Xueyu Duan, Xiaobo Liu, Ruixiang Chen, Yanjiao Pu
BACKGROUND: Protein-1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) therapy have become an important treatment approach for patients with advanced nonsmall cell lung cancer (NSCLC), but primary or secondary resistance remains a challenge for some patients. PD-1/PD-L1 combined with anti-angiogenic drugs (AAs) in NSCLC patients have potential synergistic effects, and the survival benefit may vary based on a treatment order. To investigate the efficacy of PD-1/PD-L1 combined with AAs as the treatment for patients with advanced NSCLC...
2024: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://read.qxmd.com/read/38514660/tertiary-lymphoid-structures-and-b-cells-determine-clinically-relevant-t-cell-phenotypes-in-ovarian-cancer
#3
JOURNAL ARTICLE
Lenka Kasikova, Jana Rakova, Michal Hensler, Tereza Lanickova, Jana Tomankova, Josef Pasulka, Jana Drozenova, Katerina Mojzisova, Anna Fialova, Sarka Vosahlikova, Jan Laco, Ales Ryska, Pavel Dundr, Roman Kocian, Tomas Brtnicky, Petr Skapa, Linda Capkova, Marek Kovar, Jan Prochazka, Ivan Praznovec, Vladimir Koblizek, Alice Taskova, Hisashi Tanaka, Robert Lischke, Fernando Casas Mendez, Jiri Vachtenheim, Viola Heinzelmann-Schwarz, Francis Jacob, Iain A McNeish, Michal J Halaska, Lukas Rob, David Cibula, Sandra Orsulic, Lorenzo Galluzzi, Radek Spisek, Jitka Fucikova
Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients with cancer, reflecting their contribution to the development of tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates with varying degrees of organization and maturation. Specifically, mature TLSs (mTLS) as forming only in 16% of HGSOCs with relatively elevated tumor mutational burden (TMB) are associated with an increased intratumoral density of CD8+ effector T (TEFF ) cells and TIM3+ PD1+ , hence poorly immune checkpoint inhibitor (ICI)-sensitive, CD8+ T cells...
March 21, 2024: Nature Communications
https://read.qxmd.com/read/38513890/high-throughput-antigen-microarray-identifies-longitudinal-prognostic-autoantibody-for-chemoimmunotherapy-in-advanced-non-small-cell-lung-cancer
#4
JOURNAL ARTICLE
Liyuan Dai, Qiaoyun Tan, Lin Li, Ning Lou, Cuiling Zheng, Jianliang Yang, Liling Huang, Shasha Wang, Rongrong Luo, Guangyu Fan, Tongji Xie, Jiarui Yao, Zhishang Zhang, Le Tang, Yuankai Shi, Xiaohong Han
Chemoimmunotherapy has evolved as a standard treatment for advanced non-small cell lung cancer (aNSCLC). However, inevitable drug resistance has limited its efficacy, highlighting the urgent need for biomarkers of chemoimmunotherapy. A three-phase strategy to discover, verify, and validate longitudinal predictive autoantibodies (AAbs) for aNSCLC before and after chemoimmunotherapy was employed. A total of 528 plasma samples from 267 aNSCLC patients before and after anti-PD1 immunotherapy were collected, plus 30 independent formalin-fixed paraffin-embedded samples...
March 19, 2024: Molecular & Cellular Proteomics: MCP
https://read.qxmd.com/read/38513140/pd1-inhibits-pkc%C3%AE-dependent-phosphorylation-of-cytoskeleton-related-proteins-and-immune-synapse-formation
#5
JOURNAL ARTICLE
Daniela Chmiest, Silvia Podavini, Kalliopi Ioannidou, David Vallois, Chantal Décaillet, Montserrat Gonzalez, Manfredo Quadroni, Kevin Blackney, Rebekka Schairer, Laurence L de Leval, Margot Thome
The inhibitory cell surface receptor programmed death 1 (PD1) is a major target for antibody-based cancer immunotherapies. Nevertheless, a substantial number of patients fail to respond to the treatment or experience adverse effects. An improved understanding of intracellular pathways targeted by PD1 is thus needed to develop better predictive and prognostic biomarkers. Here, via unbiased phosphoproteome analysis of primary human T cells, we demonstrate that PD1 triggering inhibited the phosphorylation and physical association with PKC theta (PKCof a variety of cytoskeleton-related proteins...
March 21, 2024: Blood Advances
https://read.qxmd.com/read/38510749/overcoming-immuno-resistance-by-rescheduling-anti-vegf-cytotoxics-anti-pd-1-combination-in-lung-cancer-model
#6
JOURNAL ARTICLE
Guillaume Sicard, Dorian Protzenko, Sarah Giacometti, Fabrice Barlési, Joseph Ciccolini, Raphaelle Fanciullino
Background: Many tumors are refractory to immune checkpoint inhibitors, but their combination with cytotoxics is expected to improve sensitivity. Understanding how and when cytotoxics best re-stimulate tumor immunity could help overcome resistance to immune checkpoint inhibitors. Methods: In vivo studies were performed in C57BL/6 mice grafted with immune-refractory LL/2 lung cancer model. A longitudinal immunomonitoring study on tumor, spleen, and blood after multiple treatments including Cisplatin, Pemetrexed, and anti-VEGF, either alone or in combination, was performed, spanning a period of up to 21 days, to determine the optimal time window during which immune checkpoint inhibitors should be added...
2024: Cancer Drug Resistance
https://read.qxmd.com/read/38509769/mait-cells-are-associated-with-responsiveness-to-neoadjuvant-immunotherapy-in-copd-associated-nsclc
#7
JOURNAL ARTICLE
Yanze Yin, Ao Zeng, Abudumijiti Abuduwayiti, Zhilong Xu, Keyi Chen, Chao Wang, Xinyun Fang, Jiarui Wang, Gening Jiang, Jie Dai
BACKGROUND: Patients with non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) experience worse clinical outcomes but respond better to immunotherapy than patients with NSCLC without COPD. Mucosal-associated invariant T (MAIT) cells, a versatile population of innate immune T lymphocytes, have a crucial function in the response to infection and tumors. This study investigated the distribution of MAIT cells in COPD-associated NSCLC and their involvement in the immune response...
March 2024: Cancer Medicine
https://read.qxmd.com/read/38452261/pembrolizumab-related-bilateral-ocular-hypotony-associated-with-ciliary-detachments-and-macula-oedema-a-treatment-resistant-side-effect
#8
JOURNAL ARTICLE
Louise Bec, Charles Khouri, Christophe Chiquet
PURPOSE: To report of a case of bilateral ocular hypotony associated with ciliary detachments and macula edema as an uncommon troublesome side-effect of pembrolizumab (an immune checkpoint inhibitor) treatment. METHODS: A 56-year-old man with a history of metastatic axillary melanoma (bone, lung, spleen and lymph node lesions) treated with pembrolizumab complained of visual deterioration at his first-year anti-PD1 follow-up visit. Visual acuity in both eyes was 20/32...
March 6, 2024: Retinal Cases & Brief Reports
https://read.qxmd.com/read/38449655/global-research-landscape-and-trends-of-cancer-radiotherapy-plus-immunotherapy-a-bibliometric-analysis
#9
JOURNAL ARTICLE
Yanhao Liu, Xu Jiang, Yujuan Wu, Haiming Yu
The aim of this study was to present current research trends on the synergistic use of radiotherapy and immunotherapy (IRT) for cancer treatment. On March 1, 2023, we conducted a literature search for IRT papers using the Web of Science database. We extracted information and constructed two databases - the Core Database (CD) with 864 papers and Generalized Database (GD) with 6344 papers. A bibliometric analysis was performed to provide insights into the research landscape, to identify emerging trends and highly cited papers and journals in the field of IRT...
March 15, 2024: Heliyon
https://read.qxmd.com/read/38440207/case-report-sudden-very-late-onset-near-fatal-pd1-inhibitor-associated-myocarditis-with-out-of-hospital-cardiac-arrest-after-2-5-years-of-pembrolizumab-treatment
#10
Richard I Lewis, Katharina Seuthe, Simon Lennartz, Jan-Phillip Weber, Nicole Kreuzberg, Karin Klingel, Paul J Bröckelmann
INTRODUCTION: Immune checkpoint inhibitors have advanced the outcomes of many different types of cancer. A rare but extraordinarily severe complication of these agents resembles immune checkpoint inhibitor-related myocarditis, which typically occurs within the first few weeks after treatment initiation with a mortality of 25%-50%. CASE REPORT: A 57-year-old woman had uneventfully received pembrolizumab for metastatic non-small cell lung cancer for over 2.5 years and was admitted after an out-of-hospital cardiac arrest due to ventricular fibrillation...
2024: Frontiers in Cardiovascular Medicine
https://read.qxmd.com/read/38439077/spatial-insights-into-immunotherapy-response-in-non-small-cell-lung-cancer-nsclc-by-multiplexed-tissue-imaging
#11
JOURNAL ARTICLE
James Monkman, Afshin Moradi, Joseph Yunis, Geoff Ivison, Aaron Mayer, Rahul Ladwa, Ken O'Byrne, Arutha Kulasinghe
The spatial localisation of immune cells within tumours are key to understand the intercellular communications that can dictate clinical outcomes. Here, we demonstrate an analysis pipeline for highly multiplexed CODEX data to phenotype and profile spatial features and interactions in NSCLC patients that subsequently received PD1 axis immunotherapy. We found that regulatory T cells (Tregs) are enriched in non-responding patients and this was consistent with their localization within stromal and peripheral tumour-margins...
March 4, 2024: Journal of Translational Medicine
https://read.qxmd.com/read/38396726/differentially-expressed-genes-involved-in-primary-resistance-to-immunotherapy-in-patients-with-advanced-stage-pulmonary-cancer
#12
JOURNAL ARTICLE
Luis Miguel Chinchilla-Tábora, Juan Carlos Montero, Luis Antonio Corchete, Idalia González-Morais, Edel Del Barco Morillo, Alejandro Olivares-Hernández, Marta Rodríguez González, José María Sayagués, María Dolores Ludeña
In the last few years, nivolumab has become the standard of care for advanced-stage lung cancer patients. Unfortunately, up to 60% of patients do not respond to this treatment. In our study, we identified variations in gene expression related to primary resistance to immunotherapy. Bronchoscopy biopsies were obtained from advanced non-small cell lung cancer (NSCLC) patients previously characterized as responders or non-responders after nivolumab treatment. Ten tumor biopsies (from three responders and seven non-responders) were analyzed by the differential expression of 760 genes using the NanoString nCounter platform...
February 8, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38379896/a-meta-analysis-of-the-efficacy-of-programmed-cell-death-1-its-ligand-inhibitors-plus-cytotoxic-t-lymphocyte-associated-antigen-4-inhibitors-in-non-small-cell-lung-cancer
#13
Li Lin, Lu Xiao, Lei Li, Chen Chen, Haorong Zhang, Changyan Yu, Lanfang Zhang, Anhua Wei, Wei Li
Background: Immune checkpoint inhibitors (ICIs), either as monotherapy or in combination with chemotherapy, have improved the therapeutic outcome for non-small cell lung cancer (NSCLC). However, the efficacy of combination therapies, such as programmed cell death 1(PD-1)/its ligand (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, in targeting different pathways remains unclear. We performed a meta-analysis to determine whether the addition of a CTLA-4 inhibitor to PD-1/PD-L1 therapy improves the efficacy of PD-1/PD-L1 monotherapy in NSCLC...
2024: Frontiers in Pharmacology
https://read.qxmd.com/read/38363451/genomic-profiling-reveals-immune-related-gene-differences-in-lung-cancer-patients-stratified-by-pd1-pdl1-expression-implications-for-immunotherapy-efficacy
#14
JOURNAL ARTICLE
Zhifeng Ye, Ting Huang, Keke Hu, HeRan Zhou, Ling Huang, Lu Wang
Lung cancer remains a leading cause of global cancer-related mortality, and the exploration of innovative therapeutic approaches, such as PD1/PDL1 immunotherapy, is critical. This study leverages comprehensive data from the Cancer Genome Atlas (TCGA) to investigate the differential expression of PD1/PDL1 in lung cancer patients and explores its implications. Clinical data, RNA expression, somatic mutations, and copy number variations of 1017 lung cancer patients were obtained from TCGA. Patients were categorized into high (HE) and low (LE) PD1/PDL1 expression groups based on mRNA levels...
February 16, 2024: Journal of Applied Genetics
https://read.qxmd.com/read/38363129/cancer-associated-fibroblast-specific-expression-of-the-matricellular-protein-ccn1-coordinates-neovascularization-and-stroma-deposition-in-melanoma-metastasis
#15
JOURNAL ARTICLE
James Hutchenreuther, John Nguyen, Katherine Quesnel, Krista M Vincent, Louis Petitjean, Sophia Bourgeois, Mark Boyd, George Bou-Gharios, Lynne-Marie Postovit, Andrew Leask
Melanoma is the leading cause of skin cancer-related death. As prognosis of melanoma patients remains problematic, identification of new therapeutic targets remains essential. Matricellular proteins are non-structural extracellular matrix proteins. They are secreted into the tumor microenvironment to coordinate behavior among different cell types, yet their contribution to melanoma is under-investigated. Examples of matricellular proteins include those comprising the CCN family. The CCN family member, CCN1, is highly pro-angiogenic...
February 16, 2024: Cancer Res Commun
https://read.qxmd.com/read/38357203/case-report-a-lung-squamous-cell-carcinoma-patient-with-a-rare-egfr-g719x-mutation-and-high-pd-l1-expression-showed-a-good-response-to-anti-pd1-therapy
#16
Zhen-Feng Zhu, Xu-Xia Bao, Hong-Yan Shi, Xi-Xi Gu
Lung cancer treatment has transitioned fully into the era of immunotherapy, yielding substantial improvements in survival rate for patients with advanced non-small cell lung cancer (NSCLC). In this report, we present a case featuring a rare epidermal growth factor receptor ( EGFR ) mutation accompanied by high programmed death-ligand 1 ( PD-L1 ) expression, demonstrating remarkable therapeutic efficacy through a combination of immunotherapy and chemotherapy. A 77-year-old male with no family history of cancer suffered from upper abdominal pain for more than half months in August 2020 and was diagnosed with stage IV (cT3N3M1c) lung squamous cell carcinoma (LUSC) harboring both a rare EGFR p...
2024: Frontiers in Oncology
https://read.qxmd.com/read/38357196/redetermination-of-pd-l1-expression-after-chemio-radiation-in-locally-advanced-pdl1-negative-nsclc-patients-retrospective-multicentric-analysis
#17
JOURNAL ARTICLE
Patrizia Ciammella, Salvatore Cozzi, Paolo Borghetti, Marco Galaverni, Valerio Nardone, Maria Paola Ruggieri, Matteo Sepulcri, Vieri Scotti, Alessio Bruni, Francesca Zanelli, Roberto Piro, Elena Tagliavini, Andrea Botti, Federico Iori, Emanuele Alì, Chiara Bennati, Marcello Tiseo
BACKGROUND: Chemoradiation therapy (CRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD1) axis inhibitors with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CRT on tumor cells programmed cell death ligand-1 (PD-L1) expression is unknown. METHODS: In this multicentric retrospective study, we analyzed paired NSCLC specimens that had been obtained pre- and post-CRT...
2024: Frontiers in Oncology
https://read.qxmd.com/read/38354688/tumor-microenvironment-tme-and-single-source-dual-energy-ct-ssdect-on-assessment-of-inconformity-between-recist1-1-and-pathological-remission-in-neoadjuvant-immunotherapy-of-nsclc
#18
JOURNAL ARTICLE
Chao Sun, Xiaobo Ma, Fanyang Meng, Xi Chen, Xu Wang, Wenyu Sun, Yinghui Xu, Hua He, Huimao Zhang, Kewei Ma
BACKGROUND: The inconformity (IC) between pathological and imaging remissions after neoadjuvant immunotherapy in patients with NSCLC can affect the evaluation of curative effect of neoadjuvant therapy and the decision regarding the chance of surgery. MATERIALS AND METHODS: Patients who achieved disease control(CR/PR/SD) after neoadjuvant chemoimmunotherapy from a clinical trial (NCT04326153) and after neoadjuvant chemotherapy during the same period were enrolled in this study...
February 13, 2024: Neoplasia: An International Journal for Oncology Research
https://read.qxmd.com/read/38349411/longitudinal-plasma-proteomic-analysis-identifies-biomarkers-and-combinational-targets-for-anti-pd1-resistant-cancer-patients
#19
JOURNAL ARTICLE
Qiaoyun Tan, Ruyun Gao, Xiaomei Zhang, Jianliang Yang, Puyuan Xing, Sheng Yang, Dan Wang, Guibing Wang, Shasha Wang, Jiarui Yao, Zhishang Zhang, Le Tang, Xiaobo Yu, Xiaohong Han, Yuankai Shi
The response rate of anti-PD1 therapy is limited, and the influence of anti-PD1 therapy on cancer patients is unclear. To address these challenges, we conducted a longitudinal analysis of plasma proteomic changes with anti-PD1 therapy in non-small cell lung cancer (NSCLC), alveolar soft part sarcoma (ASPS), and lymphoma patients. We included 339 plasma samples before and after anti-PD1 therapy from 193 patients with NSCLC, ASPS, or lymphoma. The plasma proteins were detected using data-independent acquisition-mass spectrometry and customable antibody microarrays...
February 13, 2024: Cancer Immunology, Immunotherapy: CII
https://read.qxmd.com/read/38339158/the-xcl1-mediated-dna-vaccine-targeting-type-1-conventional-dendritic-cells-combined-with-gemcitabine-and-anti-pd1-antibody-induces-potent-antitumor-immunity-in-a-mouse-lung-cancer-model
#20
JOURNAL ARTICLE
Ke Zhang, Qimuge Wuri, Zongyu Cai, Xueli Qu, Shiqi Zhang, Hui Wu, Jiaxin Wu, Chu Wang, Xianghui Yu, Wei Kong, Haihong Zhang
With the advent of cancer immunotherapy, there is a growing interest in vaccine development as a means to activate the cellular immune system against cancer. Despite the promise of DNA vaccines in this regard, their effectiveness is hindered by poor immunogenicity, leading to modest therapeutic outcomes across various cancers. The role of Type 1 conventional dendritic cells (cDC1), capable of cross-presenting vaccine antigens to activate CD8+ T cells, emerges as crucial for the antitumor function of DNA vaccines...
February 4, 2024: International Journal of Molecular Sciences
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