Renin–angiotensin–aldosterone system inhibitors and survival in patients with hypertension treated with immune checkpoint inhibitors
Zsofia D. Drobni,Olivier Michielin,Thiago Quinaglia,Daniel A. Zlotoff,Leyre Zubiri,Hannah K Gilman,Sama Supraja,Béla Merkely,V. Muller,Ryan J. Sullivan,Kerry L. Reynolds,Michael J. Pittet,Rakesh K. Jain,Tomas G. Neilan +13 more
TLDR
In this paper , the authors performed a large retrospective study of all patients treated with an ICI in a single academic network and found that concurrent use of renin-angiotensin-aldosterone system (RAAS) inhibitors was associated with better overall survival.Abstract:
Preclinical studies indicate that the concurrent use of inhibitors of the renin-angiotensin-aldosterone system (RAAS) may improve outcomes in broad groups of patients with cancer. There are limited data on the association between the use of RAAS inhibitors and outcomes among patients treated with immune checkpoint inhibitors (ICIs).We performed a retrospective study of all patients treated with an ICI in a single academic network. Of 10,903 patients, 5910 were on any anti-hypertensive medication. Of those on anti-hypertensive therapy, 3426 were prescribed a RAAS inhibitor during ICI treatment, and 2484 were prescribed other anti-hypertensive medications. The primary outcome was overall survival in the entire cohort and in sub-groups by cancer types.Thoracic cancer (34%) and melanoma (16%) were the most common types of cancer. Those prescribed a RAAS inhibitor were older, more frequently male, and had more cardiovascular risk factors. In a Cox proportional hazard model, the concurrent use of RAAS inhibitors was associated with better overall survival (hazard ratio (HR):0.92, [95% Confidence Interval (CI):0.85-0.99], P = .032). Patients with gastrointestinal (HR:0.82, [95% CI: 0.67-1.01], P = .057) and genitourinary cancer (HR:0.81, [95% CI:0.64-1.01], P = .067) had a non-statistically significant better overall survival.In this large retrospective study, patients with hypertension who were concomitantly taking a RAAS inhibitor during ICI therapy had better overall survival. This benefit was primarily noted among patients with gastrointestinal and genitourinary cancers. Prospective randomized trials are warranted to further evaluate and specify the benefit of RAAS inhibitors in patients with cancer who receive ICI therapy. read more
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Efficacy of cationic amphiphilic antihistamines on outcomes of patients treated with immune checkpoint inhibitors.
Cho-Han Chiang,Cho Hung Chiang,C. Peng,Yuan Ping Hsia,Xin Ya See,Chuan-Sheng Horng,Yuchi Chang,Xuantao Shen,Shih-Syuan Wang,Tien-Chi Tsai,Yuan-Jen Chen,Kevin Sheng-Kai Ma,Brian S. Chen,Yuxi Luan,Soon-Tzeh Tay,Chin-Hsuan Shen,Katharine Ching Chung,Cho Hsien Chiang,Cheng Ming Peng +18 more
TL;DR: In this paper , the effect of cationic amphiphilic antihistamines in patients receiving immune checkpoint inhibitors (ICIs) was evaluated in a cohort study at two tertiary referral centres in Taiwan between January 2015 and December 2021.
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Towards Immunotherapy-Induced Normalization of the Tumor Microenvironment
TL;DR: Current concepts and progress in TME normalization are summarized, including vascular normalization to reduce vessel leakiness and reprogramming of cancer-associated fibroblast to decompress vessels are summarized and considerations for combining vascular normalizing and immunotherapy efficacy are discussed.
Journal ArticleDOI
Losartan controls immune checkpoint blocker-induced edema and improves survival in glioblastoma mouse models
Meenal Datta,Sampurna Chatterjee,Elizabeth M. Perez,Simon Gritsch,Sylvie Roberge,Mark Duquette,Ivy X. Chen,Kamila Naxerova,Ashwin S. Kumar,Mitra Ghosh,Kyrre E. Emblem,Mei Rosa Ng,William Ho,Pragya Kumar,Shanmugarajan Krishnan,Xinyue Dong,Maria Carmela Speranza,Martha R. Neagu,David A. Reardon,Arlene H. Sharpe,Gordon J. Freeman,Mario L. Suvà,Lei Xu,Rakesh K. Jain +23 more
TL;DR: Losartan prevents immunotherapy-associated edema and enhances the outcome of immunotherapy in glioblastoma and identifies a “hot” tumor immune signature prior to losartan+anti-PD1 therapy that predicted long-term survival.
Journal ArticleDOI
Multiphoton Phosphorescence Quenching Microscopy Reveals Kinetics of Tumor Oxygenation during Antiangiogenesis and Angiotensin Signaling Inhibition
TL;DR: In this paper , the authors developed a multiphoton phosphorescence quenching microscopy system using a low-molecular-weight palladium porphyrin probe to measure perfused vessels, oxygen tension, and their spatial correlations in vivo in mouse skin, bone marrow, and four different tumor models.
Posted ContentDOI
Addition of losartan to FOLFORINOX and chemoradiation downregulates pro-invasion and immunosuppression-associated genes in locally advanced pancreatic cancer
Yves Boucher,Jessica M. Posada,Sumit K. Subudhi,Spencer Rosario,Lin Gu,A Sarath Kumar,Heena Kumra,Mari Mino-Kenudson,Nilesh Talele,Dan G. Duda,Dai Fukumura,Jana Yim-Hung Wo,J. Clark,David P. Ryan,Carlos Fernandez-del Castillo,Theodore S. Hong,M. Pittet,Rajul K. Jain +17 more
TL;DR: Adding losartan to FFX+CRT reduced pro-invasion and immunosuppression related genes, which were associated with improved treatment outcomes in patients with LAPC.
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