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/38532632/m6a-mediated-molecular-patterns-and-tumor-microenvironment-infiltration-characterization-in-nasopharyngeal-carcinoma
#2
JOURNAL ARTICLE
Yong Wang, Lisha Peng, Feng Wang
N6-methyladenosine (m6A) is the most predominant RNA epigenetic regulation in eukaryotic cells. Numerous evidence revealed that m6A modification exerts a crucial role in the regulation of tumor microenvironment (TME) cell infiltration in several tumors. Nevertheless, the potential role and mechanism of m6A modification in nasopharyngeal carcinoma (NPC) remains unknown. mRNA expression data and clinical information from GSE102349, and GSE53819 datasets obtained from Gene Expression Omnibus (GEO) was used for differential gene expression and subsequent analysis...
December 31, 2024: Cancer Biology & Therapy
https://read.qxmd.com/read/38521617/avelumab-plus-intermittent-axitinib-in-previously-untreated-patients-with-metastatic-renal-cell-carcinoma-the-tide-a-phase-2-study
#3
JOURNAL ARTICLE
Roberto Iacovelli, Chiara Ciccarese, Sebastiano Buti, Paolo Andrea Zucali, Emanuela Fantinel, Davide Bimbatti, Elena Verzoni, Caterina Accettura, Lucia Bonomi, Consuelo Buttigliero, Giuseppe Fornarini, Stefania Pipitone, Francesco Atzori, Cristina Masini, Francesco Massari, Francesca Primi, Alessandro Strusi, Giulia Claire Giudice, Matteo Perrino, Marco Maruzzo, Michele Milella, Diana Giannarelli, Matteo Brunelli, Giuseppe Procopio, Giampaolo Tortora
BACKGROUND: Combinations of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitor (ICI) against PD1/PD-L1 are the standard first-line therapy for patients with metastatic renal cell carcinoma (mRCC), irrespective of the prognostic class. OBJECTIVE: To investigate the feasibility and safety of withdrawing VEGFR-TKI but continuing anti-PD1/PD-L1 in patients who achieve a response to their combination...
March 22, 2024: European Urology
https://read.qxmd.com/read/38520742/cancers-of-unknown-primary-origin-real-world-clinical-outcomes-and-genomic-analysis-at-the-european-institute-of-oncology
#4
JOURNAL ARTICLE
Luca Boscolo Bielo, Carmen Belli, Edoardo Crimini, Matteo Repetto, Liliana Ascione, Gloria Pellizzari, Celeste Santoro, Valeria Fuorivia, Massimo Barberis, Nicola Fusco, Elena Guerini Rocco, Giuseppe Curigliano
BACKGROUND: Cancer of unknown primary origin (CUP) poses a significant challenge due to poor clinical outcomes and limited treatment options. As such, further definition of clinicopathological factors and genomic profile to better adapt treatment strategies is required. METHODS: Medical records were interrogated to retrospectively include CUP with available clinical and genomics data at the European Institute of Oncology. Next-generation sequencing (NGS) included targeted panels...
March 23, 2024: Oncologist
https://read.qxmd.com/read/38515568/immune-checkpoint-inhibitor-related-acquired-amegakaryocytosis-thrombocytopenia-a-case-report-and-literature-review
#5
Valérian Rivet, Vincent Sibaud, Jérémie Dion, Thibaut Volosov, Mélanie Biteau, Andréa Pastissier, Karen Delavigne, Pierre Cougoul, Odile Rauzy, Thibault Comont
INTRODUCTION: Immune checkpoint inhibitors (ICIs) are used in several advanced malignancies and may cause various immune-related adverse events (irAEs). Among them, hematological irAEs are less described. Acquired amegakaryocytic thrombocytopenia (AAT) is a rare immune hematologic disorder characterized by severe thrombocytopenia and complete absence of megakaryocytes in bone marrow. CASE PRESENTATION: Herein, we present the case of a patient in their 40s with metastatic melanoma who developed an AAT after 12 cycles of nivolumab (anti-PD1)...
2024: Frontiers in Oncology
https://read.qxmd.com/read/38513890/high-throughput-antigen-microarray-identifies-longitudinal-prognostic-autoantibody-for-chemoimmunotherapy-in-advanced-non-small-cell-lung-cancer
#6
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/38510749/overcoming-immuno-resistance-by-rescheduling-anti-vegf-cytotoxics-anti-pd-1-combination-in-lung-cancer-model
#7
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
#8
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/38508217/wtap-induced-n-6-methyladenosine-of-pd-l1-blocked-t-cell-mediated-antitumor-activity-under-hypoxia-in-colorectal-cancer
#9
JOURNAL ARTICLE
Qi-Zhi Liu, Nan Zhang, Jun-Yi Chen, Min-Jun Zhou, De-Hua Zhou, Zhuo Chen, Zhen-Xing Huang, Yu-Xiang Xie, Guang-Lei Qiao, Xiao-Huang Tu
N6 -Methyladenosine (m6 A) is a important process regulating gene expression post-transcriptionally. Programmed death ligand 1 (PD-L1) is a major immune inhibitive checkpoint that facilitates immune evasion and is expressed in tumor cells. In this research we discovered that Wilms' tumor 1-associated protein (WTAP) degradation caused by ubiquitin-mediated cleavage in cancer cells (colorectal cancer, CRC) under hypoxia was inhibited by Pumilio homolog 1 (PUM1) directly bound to WTAP. WTAP enhanced PD-L1 expression in a way that was m6 A-dependent...
March 20, 2024: Cancer Science
https://read.qxmd.com/read/38504270/unveiling-cxcr2-as-a-promising-therapeutic-target-in-renal-cell-carcinoma-exploring-the-immunotherapeutic-paradigm-shift-through-its-inhibition-by-rct001
#10
JOURNAL ARTICLE
Christopher Montemagno, Arnaud Jacquel, Charlotte Pandiani, Olivia Rastoin, Rosie Dawaliby, Thomas Schmitt, Maxence Bourgoin, Héliciane Palenzuela, Anne-Laure Rossi, Damien Ambrosetti, Jerome Durivault, Frederic Luciano, Delphine Borchiellini, Julie Le Du, Leticia Christina Pires Gonçalves, Patrick Auberger, Rachid Benhida, Lisa Kinget, Benoit Beuselinck, Cyril Ronco, Gilles Pagès, Maeva Dufies
BACKGROUND: In clear cell renal cell carcinoma (ccRCC), first-line treatment combines nivolumab (anti-PD-1) and ipilimumab (anti-CTLA4), yielding long-term remissions but with only a 40% success rate. Our study explored the potential of enhancing ccRCC treatment by concurrently using CXCR2 inhibitors alongside immunotherapies. METHODS: We analyzed ELR + CXCL levels and their correlation with patient survival during immunotherapy. RCT001, a unique CXCR2 inhibitor, was examined for its mechanism of action, particularly its effects on human primary macrophages...
March 19, 2024: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/38500886/intratumor-tertiary-lymphatic-structure-evaluation-predicts-the-prognosis-and-immunotherapy-response-of-patients-with-colorectal-cancer
#11
JOURNAL ARTICLE
Huijing Feng, Siyuan Zhang, Qiuru Zhou, Fei Han, Gang Du, Lin Wang, Xuena Yang, Xiying Zhang, Wenwen Yu, Feng Wei, Xishan Hao, Xiubao Ren, Hua Zhao
BACKGROUND: Immune checkpoint therapy, involving the programmed cell death 1 (PD-1) monoclonal antibody, has revolutionized the treatment of cancer. Tertiary lymphatic structure (TLS) serves as an immune indicator to predict the efficacy of PD-1 antibody therapy. However, there is no clear result whether the distribution, quantity, and maturity of TLS can be effective indicators for predicting the clinical efficacy of anti-PD1 immunotherapy in patients with colorectal cancer (CRC). METHODS: Fifty-seven patients who underwent surgical resection and thirty-nine patients who received anti-PD-1 immunotherapy were enrolled in this retrospective study...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38500667/influence-of-intestinal-microbial-metabolites-on-the-abscopal-effect-after-radiation-therapy-combined-with-immune-checkpoint-inhibitors
#12
JOURNAL ARTICLE
Hannah Felchle, Julia Gissibl, Laura Lansink Rotgerink, Sophie M Nefzger, Caroline N Walther, Vincent R Timnik, Stephanie E Combs, Julius C Fischer
BACKGROUND: Most clinical studies failed to elicit a strong antitumor immune response and subsequent systemic tumor regression after radiation therapy (RT), even in combination with the immune checkpoint inhibitors (ICI) anti-CTLA4 or anti-PD1. Mechanistically, type I interferon (IFN-I) activation is essential for the development of such abscopal effects (AE); however, mechanisms driving or limiting IFN-I activation are ill defined. Groundbreaking discoveries have shown that antibiotics (ABx) can affect oncological outcomes and that microbiota-derived metabolites can modulate systemic antitumor immunity...
May 2024: Clinical and Translational Radiation Oncology
https://read.qxmd.com/read/38493679/the-effect-of-a-single-dose-of-nivolumab-prior-to-isolated-limb-perfusion-for-patients-with-in-transit-melanoma-metastases-an-interim-analysis-of-a-phase-ib-ii-randomized-double-blind-placebo-controlled-trial-nivoilp-trial
#13
JOURNAL ARTICLE
Carl-Jacob Holmberg, Lisanne P Zijlker, Dimitrios Katsarelias, Anne E Huibers, Michel W J M Wouters, Yvonne Schrage, Sophie J M Reijers, Johannes V van Thienen, Dirk J Grünhagen, Anna Martner, Jonas A Nilsson, Alexander C J van Akkooi, Lars Ny, Winan J van Houdt, Roger Olofsson Bagge
OBJECTIVE: ILP has shown to achieve high response rates in patients with melanoma ITM. Possibly there is a synergistic mechanism of action of ILP and anti-PD1. The aim of this trial was to investigate the safety and efficacy of adding a single dose of systemic anti-PD1 to isolated limb perfusion (ILP) for patients with melanoma in-transit metastases (ITM). METHODS: In this placebo controlled double-blind phase Ib/II trial, patients with melanoma ITM were randomized 1:1 to either a single systemic dose of nivolumab or placebo one day prior to ILP...
March 12, 2024: European Journal of Surgical Oncology
https://read.qxmd.com/read/38478666/linear-iga-bullous-dermatosis-associated-with-immunotherapy
#14
JOURNAL ARTICLE
Bahar Momin, Tue F Nguyen, Daniel Glade, Alison Messer
Linear IgA bullous dermatosis (LABD) is a rare mucocutaneus blistering autoimmune disease caused by IgA autoantibodies. Its clinical manifestation can be indistinguishable from bullous pemphigoid (BP), a similar autoimmune bullous disease caused by IgG and IgE autoantibodies. Although BP has been reported as an adverse cutaneous effect of immunotherapy, LABD has rarely been associated with immunotherapy in the literature. We present the case of a 67-year-old woman with metastatic ovarian cancer receiving anti-PD1 and anti-CTLA4 with new onset pruritic tense bullae to the trunk, hands, elbows (in annular distribution) that occurred after immunotherapy...
December 15, 2023: Dermatology Online Journal
https://read.qxmd.com/read/38473329/anti-pd-1-therapy-in-advanced-pediatric-malignancies-in-nationwide-study-good-outcome-in-skin-melanoma-and-hodgkin-lymphoma
#15
JOURNAL ARTICLE
Agata Marjańska, Katarzyna Pawińska-Wąsikowska, Aleksandra Wieczorek, Monika Drogosiewicz, Bożenna Dembowska-Bagińska, Katarzyna Bobeff, Wojciech Młynarski, Katarzyna Adamczewska-Wawrzynowicz, Jacek Wachowiak, Małgorzata A Krawczyk, Ninela Irga-Jaworska, Jadwiga Węcławek-Tompol, Krzysztof Kałwak, Małgorzata Sawicka-Żukowska, Maryna Krawczuk-Rybak, Anna Raciborska, Agnieszka Mizia-Malarz, Agata Sobocińska-Mirska, Paweł Łaguna, Walentyna Balwierz, Jan Styczyński
BACKGROUND/AIM: The role of immune checkpoint inhibitors (ICIs; anti-PD1) in the treatment of childhood cancers is still evolving. The aim of this nationwide retrospective study was to assess the safety and effectiveness of ICIs used in a group of 42 patients, with a median age of 13.6 years, with various types of advanced malignancies treated in pediatric oncology centers in Poland between 2015 and 2023. RESULTS: The indications for treatment with anti-PD1 were as follows: Hodgkin lymphoma (11); malignant skin melanoma (9); neuroblastoma (8); and other malignancies (14)...
February 28, 2024: Cancers
https://read.qxmd.com/read/38473262/the-efficacy-and-safety-of-immune-checkpoint-inhibitors-in-adrenocortical-carcinoma-a-systematic-review-and-meta-analysis
#16
REVIEW
Obada Ababneh, Alina Ghazou, Mohmmad Alawajneh, Saleh Alhaj Mohammad, Abdullah Bani-Hani, Nasr Alrabadi, Aditya Shreenivas
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of different malignancies. However, their efficacy in advanced adrenocortical carcinoma (ACC) remains uncertain. Thus, we conducted a systematic review and meta-analysis to summarize the efficacy and tolerability of ICIs in patients with advanced ACC. We searched PubMed, Scopus, and CENTRAL for studies that used ICIs in ACC. Studies with more than five patients were included in the meta-analysis of the objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and grade 3/4 adverse events...
February 23, 2024: Cancers
https://read.qxmd.com/read/38473217/thermal-ablation-combined-with-immune-checkpoint-blockers-a-10-year-monocentric-experience
#17
JOURNAL ARTICLE
Baptiste Bonnet, Louis Tournier, Frédéric Deschamps, Steven Yevich, Aurélien Marabelle, Caroline Robert, Laurence Albiges, Benjamin Besse, Victoire Bonnet, Thierry De Baère, Lambros Tselikas
PURPOSE: We report a 10-year experience in cancer therapy with concomitant treatment of percutaneous thermal ablation (PTA) and immune checkpoint blockers (ICBs). MATERIAL AND METHODS: This retrospective cohort study included all patients at a single tertiary cancer center who had received ICBs at most 90 days before, or 30 days after, PTA. Feasibility and safety were assessed as the primary outcomes. The procedure-related complications and immune-related adverse events (irAEs) were categorized according to the Common Terminology Criteria for Adverse Events v5...
February 21, 2024: Cancers
https://read.qxmd.com/read/38473216/real-world-data-on-clinical-outcomes-and-treatment-management-of-advanced-melanoma-patients-single-center-study-of-a-tertiary-cancer-center-in-switzerland
#18
JOURNAL ARTICLE
Ramon Staeger, Julia M Martínez-Gómez, Patrick Turko, Egle Ramelyte, Lukas Kraehenbuehl, Valerio Del Prete, Omar Hasan Ali, Mitchell P Levesque, Reinhard Dummer, Mirjam C Nägeli, Joanna Mangana
BACKGROUND: Immune checkpoint inhibitors (ICIs) and BRAF/MEK inhibitors (BRAF/MEKi) have drastically changed the outcomes of advanced melanoma patients in both the resectable/adjuvant and unresectable/metastatic setting. In this follow-up analysis of real-world data, we aimed to investigate the clinical management and outcomes of advanced melanoma patients in a tertiary referral center in Switzerland approximately a decade after the introduction of ICIs and BRAF/MEKi into clinical use...
February 20, 2024: Cancers
https://read.qxmd.com/read/38467181/intratumoral-injection-of-interferon-gamma-promotes-the-efficacy-anti-pd1-treatment-in-colorectal-cancer
#19
JOURNAL ARTICLE
Yang Tang, Jingsun Wei, Xiaoxu Ge, Chengxuan Yu, Wei Lu, Yucheng Qian, Hang Yang, Dongliang Fu, Yimin Fang, Yinyi Zhou, Zhanhuai Wang, Qian Xiao, Kengfeng Ding
Immune checkpoint inhibitors (ICIs) offer new options for the treatment of patients with solid cancers worldwide. The majority of colorectal cancers (CRC) are proficient in mismatch-repair (pMMR) genes, harbors few tumor antigens and is insensitive to ICIs. These tumors are often found to be immune-deserted. We hypothesized that forcing immune cell infiltration into the tumor microenvironment followed by immune ignition by PD1 blockade may initiate a positive immune cycle that can boost antitumor immunity. Bioinformatics using a public database suggested that IFNγ was a key indicator of immune status and prognosis in CRC...
March 9, 2024: Cancer Letters
https://read.qxmd.com/read/38463391/a-phase-1-trial-of-human-telomerase-reverse-transcriptase-htert-vaccination-combined-with-therapeutic-strategies-to-control-immune-suppressor-mechanisms
#20
JOURNAL ARTICLE
Nahid Zareian, Oleg Eremin, Hardev Pandha, Richard Baird, Vineet Kwatra, Gabriel Funingana, Chandan Verma, Desmond Choy, Steven Hargreaves, Pejvak Moghimi, Adrian Shepherd, Dileep N Lobo, Jennifer Eremin, Farzin Farzaneh, Shahram Kordasti, James Spicer
The presence of inhibitory immune cells and difficulty in generating activated effector T cells remain obstacles to development of effective cancer vaccines. We designed a vaccine regimen combining human telomerase reverse transcriptase (hTERT) peptides with concomitant therapies targeting regulatory T cells (Tregs) and cyclooxygenase-2 (COX2)-mediated immunosuppression. This Phase 1 trial combined an hTERT-derived 7-peptide library, selected to ensure presentation by both HLA class-I and class-II in 90% of patients, with oral low-dose cyclophosphamide (to modulate Tregs) and the COX2 inhibitor celecoxib...
2024: Experimental Biology and Medicine
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