Evidence map›Paper›PMID 38322766›Full record

ArticleFrontiers in cardiovascular medicine2024

Combinatorial immune checkpoint blockade increases myocardial expression of NLRP-3 and secretion of H-FABP, NT-Pro-BNP, interleukin-1β and interleukin-6: biochemical implications in cardio-immuno-oncology.

V Quagliariello, M Passariello, I Bisceglia, A Paccone, A Inno, C Maurea, R Rapuano Lembo, L Manna, M Iovine, M L Canale and 5 more

Abstract read
In one paragraph

Article in Frontiers in cardiovascular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

V QuagliarielloDivision of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.
M PassarielloDepartment of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy.
I BiscegliaServizi Cardiologici Integrati, Dipartimento Cardio-Toraco-Vascolare, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy.
A PacconeDivision of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.
A InnoMedical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Sacro Cuore Don Calabria, Negrar, Italy.
C MaureaMedical Oncology, Ospedale del Mare, Naples, Italy.
R Rapuano LemboDepartment of Molecular Medicine, Ceinge-Biotecnologie Avanzate s.c.a.r.l., Naples, Italy.
L MannaDepartment of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy.
M IovineDivision of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.
M L CanaleU.O.C. Cardiologia, Ospedale Versilia, Lido di Camaiore (LU), Camaiore, Italy.
M ScherilloCardiologia Interventistica e UTIC, A.O. San Pio, Presidio Ospedaliero Gaetano Rummo, Benevento, Italy.
P A AsciertoMelanoma Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale", Naples, Italy.
D GabrielliU.O.C. Cardiologia, Dipartimento Cardio-Toraco-Vascolare, Azienda Ospedaliera San Camillo Forlanini, Roma - Fondazione per il Tuo Cuore - Heart Care Foundation, Firenze, Italy.
C De LorenzoDepartment of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy.
N MaureaDivision of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Immune checkpoint blockade in monotherapy or combinatorial regimens with chemotherapy or radiotherapy have become an integral part of oncology in recent years. Monoclonal antibodies against CTLA-4 or PD-1 or PDL-1 are the most studied ICIs in randomized clinical trials, however, more recently, an anti-LAG3 (Lymphocyte activation gene-3) antibody, Relatlimab, has been approved by FDA in combination with Nivolumab for metastatic melanoma therapy. Moreover, Atezolizumab is actually under study in association with Ipilimumab for therapy of metastatic lung cancer. Myocarditis, vasculitis and endothelitis are rarely observed in these patients on monotherapy, however new combination therapies could expose patients to more adverse cardiovascular events. Methods: Human cardiomyocytes co-cultured with human peripheral blood lymphocytes (hPBMCs) were exposed to monotherapy and combinatorial ICIs (PD-L1 and CTLA-4 or PD-1 and LAG-3 blocking agents, at 100 nM) for 48 h. After treatments, cardiac cell lysis and secretion of biomarkers of cardiotoxicity (H-FABP, troponin-T, BNP, NT-Pro-BNP), NLRP3-inflammasome and Interleukin 1 and 6 were determined through colorimetric and enzymatic assays. Mitochondrial functions were studied in cardiomyocyte cell lysates through quantification of intracellular Ca Results: Both combinations of immune checkpoint inhibitors exert more potent cardiotoxic side effects compared to monotherapies against human cardiac cells co-cultured with human lymphocytes. LDH release from cardiac cells was 43% higher in PD-L1/CTLA-4 blocking agents, and 35.7% higher in PD-1/LAG-3 blocking agents compared to monotherapies. HDAC4 and intracellular Ca Conclusions: Data of the present study, although

Indexed as

cancercardiologycardiotoxicityimmune checkpoint inhibitorsinflammationmyocarditisoncology

Identifiers

PMID38322766
PMCPMC10844473

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.