Immune checkpoint blockade therapy mitigates systemic inflammation and affects cellular FLIP-expressing monocytic myeloid-derived suppressor cells in non-progressor non-small cell lung cancer patients.

Autor:	Adamo A; Immunology section, Department of Medicine University and Hospital Trust of Verona, Verona, Italy., Frusteri C; Immunology section, Department of Medicine University and Hospital Trust of Verona, Verona, Italy., Pilotto S; Oncology section, Department of Engineering for Innovative Medicine and Hospital Trust of Verona, Verona, Italy., Caligola S; Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IOV-IRCCS), Padova, Italy., Belluomini L; Oncology section, Department of Engineering for Innovative Medicine and Hospital Trust of Verona, Verona, Italy., Poffe O; Immunology section, Department of Medicine University and Hospital Trust of Verona, Verona, Italy., Giacobazzi L; Immunology section, Department of Medicine University and Hospital Trust of Verona, Verona, Italy., Dusi S; Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IOV-IRCCS), Padova, Italy., Musiu C; Immunology section, Department of Medicine University and Hospital Trust of Verona, Verona, Italy., Hu Y; Immunology section, Department of Medicine University and Hospital Trust of Verona, Verona, Italy., Wang T; Immunology section, Department of Medicine University and Hospital Trust of Verona, Verona, Italy., Rizzini D; Immunology section, Department of Medicine University and Hospital Trust of Verona, Verona, Italy., Vella A; Immunology section, Department of Medicine University and Hospital Trust of Verona, Verona, Italy., Canè S; Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IOV-IRCCS), Padova, Italy., Sartori G; Oncology section, Department of Engineering for Innovative Medicine and Hospital Trust of Verona, Verona, Italy., Insolda J; Oncology section, Department of Engineering for Innovative Medicine and Hospital Trust of Verona, Verona, Italy., Sposito M; Oncology section, Department of Engineering for Innovative Medicine and Hospital Trust of Verona, Verona, Italy., Incani UC; Oncology section, Department of Engineering for Innovative Medicine and Hospital Trust of Verona, Verona, Italy., Carbone C; Medical Oncology, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy., Piro G; Medical Oncology, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy., Pettinella F; General Pathology section, Department of Medicine University of Verona, Verona, Italy., Qi F; Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, P.R. China., Wang D; Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, P.R. China., Sartoris S; Immunology section, Department of Medicine University and Hospital Trust of Verona, Verona, Italy., De Sanctis F; Immunology section, Department of Medicine University and Hospital Trust of Verona, Verona, Italy., Scapini P; General Pathology section, Department of Medicine University of Verona, Verona, Italy., Dusi S; General Pathology section, Department of Medicine University of Verona, Verona, Italy., Cassatella MA; General Pathology section, Department of Medicine University of Verona, Verona, Italy., Bria E; Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IOV-IRCCS), Padova, Italy., Milella M; Oncology section, Department of Engineering for Innovative Medicine and Hospital Trust of Verona, Verona, Italy., Bronte V; Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IOV-IRCCS), Padova, Italy., Ugel S; Immunology section, Department of Medicine University and Hospital Trust of Verona, Verona, Italy.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2023 Sep 14; Vol. 12 (1), pp. 2253644. Date of Electronic Publication: 2023 Sep 14 (Print Publication: 2023).
DOI:	10.1080/2162402X.2023.2253644
Abstrakt:	Cancer cells favor the generation of myeloid cells with immunosuppressive and inflammatory features, including myeloid-derived suppressor cells (MDSCs), which support tumor progression. The anti-apoptotic molecule, cellular FLICE (FADD-like interleukin-1β-converting enzyme)-inhibitory protein (c-FLIP), which acts as an important modulator of caspase-8, is required for the development and function of monocytic (M)-MDSCs. Here, we assessed the effect of immune checkpoint inhibitor (ICI) therapy on systemic immunological landscape, including FLIP-expressing MDSCs, in non-small cell lung cancer (NSCLC) patients. Longitudinal changes in peripheral immunological parameters were correlated with patients' outcome. In detail, 34 NSCLC patients were enrolled and classified as progressors (P) or non-progressors (NP), according to the RECIST evaluation. We demonstrated a reduction in pro-inflammatory cytokines such as IL-8, IL-6, and IL-1β in only NP patients after ICI treatment. Moreover, using t -distributed stochastic neighbor embedding ( t -SNE) and cluster analysis, we characterized in NP patients a significant increase in the amount of lymphocytes and a slight contraction of myeloid cells such as neutrophils and monocytes. Despite this moderate ICI-associated alteration in myeloid cells, we identified a distinctive reduction of c-FLIP expression in M-MDSCs from NP patients concurrently with the first clinical evaluation (T1), even though NP and P patients showed the same level of expression at baseline (T0). In agreement with the c-FLIP expression, monocytes isolated from both P and NP patients displayed similar immunosuppressive functions at T0; however, this pro-tumor activity was negatively influenced at T1 in the NP patient cohort exclusively. Hence, ICI therapy can mitigate systemic inflammation and impair MDSC-dependent immunosuppression. Competing Interests: No potential conflict of interest was reported by the author(s). (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Databáze:	MEDLINE
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