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Immune-related toxicity and soluble profile in patients affected by solid tumors: a network approach.
Botticelli, Andrea; Cirillo, Alessio; Pomati, Giulia; Cortesi, Enrico; Rossi, Ernesto; Schinzari, Giovanni; Tortora, Giampaolo; Tomao, Silverio; Fiscon, Giulia; Farina, Lorenzo; Scagnoli, Simone; Pisegna, Simona; Ciurluini, Fabio; Chiavassa, Antonella; Amirhassankhani, Sasan; Ceccarelli, Fulvia; Conti, Fabrizio; Di Filippo, Alessandra; Zizzari, Ilaria Grazia; Napoletano, Chiara; Rughetti, Aurelia; Nuti, Marianna; Mezi, Silvia; Marchetti, Paolo.
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  • 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.
  • Tortora G; Medical Oncology, Università Cattolica del Sacro Cuore, 00168, Rome, Italy.
  • Tomao S; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168, Rome, Italy.
  • Fiscon G; Medical Oncology, Università Cattolica del Sacro Cuore, 00168, Rome, Italy.
  • Farina L; Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy.
  • Scagnoli S; Department of Computer, Control, and Management Engineering "Antonio Ruberti", Sapienza University of Rome, Via Ariosto 25, 00185, Rome, Italy.
  • Pisegna S; Department of Computer, Control, and Management Engineering "Antonio Ruberti", Sapienza University of Rome, Via Ariosto 25, 00185, Rome, Italy.
  • Ciurluini F; Department of Medical and Surgical Sciences and Translational Medicine, University of Rome "Sapienza", 00185, Rome, Italy.
  • Chiavassa A; Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy.
  • Amirhassankhani S; Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy.
  • Ceccarelli F; Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy.
  • Conti F; Guy's and St Thomas' NHS Foundation Trust, Westminster Bridge Rd, Bishop's, London, SE1 7EH, UK.
  • Di Filippo A; Arthritis Center, Dipartimento Di Scienze Cliniche Internistiche, Anestesiologiche E Cardiovascolari, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
  • Zizzari IG; Arthritis Center, Dipartimento Di Scienze Cliniche Internistiche, Anestesiologiche E Cardiovascolari, Sapienza University of Rome, Viale del Policlinico 155, 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; Laboratory of Tumor Immunology and Cell Therapy, Department of Experimental Medicine, Policlinico Umberto I, University of Rome "Sapienza", 00161, Rome, Italy.
  • Marchetti P; Laboratory of Tumor Immunology and Cell Therapy, Department of Experimental Medicine, Policlinico Umberto I, University of Rome "Sapienza", 00161, Rome, Italy.
Cancer Immunol Immunother ; 72(7): 2217-2231, 2023 Jul.
Article en En | MEDLINE | ID: mdl-36869232
ABSTRACT

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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Antineoplásicos Inmunológicos / Neoplasias Tipo de estudio: Clinical_trials / Observational_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Cancer Immunol Immunother Asunto de la revista: ALERGIA E IMUNOLOGIA / NEOPLASIAS / TERAPEUTICA Año: 2023 Tipo del documento: Article País de afiliación: Italia
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Antineoplásicos Inmunológicos / Neoplasias Tipo de estudio: Clinical_trials / Observational_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Cancer Immunol Immunother Asunto de la revista: ALERGIA E IMUNOLOGIA / NEOPLASIAS / TERAPEUTICA Año: 2023 Tipo del documento: Article País de afiliación: Italia