Immune-related toxicity and soluble profile in patients affected by solid tumors: a network approach.

Autor: Botticelli A; Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy., Cirillo A; Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy. alessio.cirillo@uniroma1.it., Pomati G; Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161, Rome, Italy., Cortesi E; Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy., Rossi E; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168, Rome, Italy., Schinzari G; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168, Rome, Italy.; Medical Oncology, Università Cattolica del Sacro Cuore, 00168, Rome, Italy., Tortora G; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168, Rome, Italy.; Medical Oncology, Università Cattolica del Sacro Cuore, 00168, Rome, Italy., Tomao S; Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy., Fiscon G; Department of Computer, Control, and Management Engineering 'Antonio Ruberti', Sapienza University of Rome, Via Ariosto 25, 00185, Rome, Italy., Farina L; Department of Computer, Control, and Management Engineering 'Antonio Ruberti', Sapienza University of Rome, Via Ariosto 25, 00185, Rome, Italy., Scagnoli S; Department of Medical and Surgical Sciences and Translational Medicine, University of Rome 'Sapienza', 00185, Rome, Italy., Pisegna S; Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy., Ciurluini F; Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy., Chiavassa A; Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy., Amirhassankhani S; Guy's and St Thomas' NHS Foundation Trust, Westminster Bridge Rd, Bishop's, London, SE1 7EH, UK., Ceccarelli F; Arthritis Center, Dipartimento Di Scienze Cliniche Internistiche, Anestesiologiche E Cardiovascolari, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy., Conti F; Arthritis Center, Dipartimento Di Scienze Cliniche Internistiche, Anestesiologiche E Cardiovascolari, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy., Di Filippo A; Laboratory of Tumor Immunology and Cell Therapy, Department of Experimental Medicine, Policlinico Umberto I, University of Rome 'Sapienza', 00161, Rome, Italy., Zizzari IG; Laboratory of Tumor Immunology and Cell Therapy, Department of Experimental Medicine, Policlinico Umberto I, University of Rome 'Sapienza', 00161, Rome, Italy., Napoletano C; Laboratory of Tumor Immunology and Cell Therapy, Department of Experimental Medicine, Policlinico Umberto I, University of Rome 'Sapienza', 00161, Rome, Italy., Rughetti A; Laboratory of Tumor Immunology and Cell Therapy, Department of Experimental Medicine, Policlinico Umberto I, University of Rome 'Sapienza', 00161, Rome, Italy., Nuti M; Laboratory of Tumor Immunology and Cell Therapy, Department of Experimental Medicine, Policlinico Umberto I, University of Rome 'Sapienza', 00161, Rome, Italy., Mezi S; Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy., Marchetti P; Istituto Dermopatico Dell'Immacolata, 00167, Rome, Italy.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2023 Jul; Vol. 72 (7), pp. 2217-2231. Date of Electronic Publication: 2023 Mar 03.
DOI: 10.1007/s00262-023-03384-9
Abstrakt: Background: Immune checkpoint inhibitors (ICIs) have particular, immune-related adverse events (irAEs), as a consequence of interfering with self-tolerance mechanisms. The incidence of irAEs varies depending on ICI class, administered dose and treatment schedule. The aim of this study was to define a baseline (T0) immune profile (IP) predictive of irAE development.
Methods: A prospective, multicenter study evaluating the immune profile (IP) of 79 patients with advanced cancer and treated with anti-programmed cell death protein 1 (anti-PD-1) drugs as a first- or second-line setting was performed. The results were then correlated with irAEs onset. The IP was studied by means of multiplex assay, evaluating circulating concentration of 12 cytokines, 5 chemokines, 13 soluble immune checkpoints and 3 adhesion molecules. Indoleamine 2, 3-dioxygenase (IDO) activity was measured through a modified liquid chromatography-tandem mass spectrometry using the high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. A connectivity heatmap was obtained by calculating Spearman correlation coefficients. Two different networks of connectivity were constructed, based on the toxicity profile.
Results: Toxicity was predominantly of low/moderate grade. High-grade irAEs were relatively rare, while cumulative toxicity was high (35%). Positive and statistically significant correlations between the cumulative toxicity and IP10 and IL8, sLAG3, sPD-L2, sHVEM, sCD137, sCD27 and sICAM-1 serum concentration were found. Moreover, patients who experienced irAEs had a markedly different connectivity pattern, characterized by disruption of most of the paired connections between cytokines, chemokines and connections of sCD137, sCD27 and sCD28, while sPDL-2 pair-wise connectivity values seemed to be intensified. Network connectivity analysis identified a total of 187 statistically significant interactions in patients without toxicity and a total of 126 statistically significant interactions in patients with toxicity. Ninety-eight interactions were common to both networks, while 29 were specifically observed in patients who experienced toxicity.
Conclusions: A particular, common pattern of immune dysregulation was defined in patients developing irAEs. This immune serological profile, if confirmed in a larger patient population, could lead to the design of a personalized therapeutic strategy in order to prevent, monitor and treat irAEs at an early stage.
(© 2023. The Author(s).)
Databáze: MEDLINE
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