Transcutaneous Vagal Nerve Stimulation Alone or in Combination With Radiotherapy Stimulates Lung Tumor Infiltrating Lymphocytes But Fails to Suppress Tumor Growth.

Autor:	Reijmen E; Laboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit Brussel, Brussels, Belgium., De Mey S; Department of Radiotherapy, Oncology Centre University Hospital Brussels (Universitair Ziekenhuis (UZ) Brussel), Brussels, Belgium., Van Damme H; Myeloid Cell Immunology Lab, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., De Ridder K; Laboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit Brussel, Brussels, Belgium., Gevaert T; Department of Radiotherapy, Oncology Centre University Hospital Brussels (Universitair Ziekenhuis (UZ) Brussel), Brussels, Belgium., De Blay E; Cell Differentiation Lab, Vrije Universiteit Brussel, Brussels, Belgium., Bouwens L; Cell Differentiation Lab, Vrije Universiteit Brussel, Brussels, Belgium., Collen C; Department of Radiotherapy, Oncology Centre University Hospital Brussels (Universitair Ziekenhuis (UZ) Brussel), Brussels, Belgium., Decoster L; Laboratory of Medical and Molecular Oncology (LMMO), Department of Medical Oncology, Oncologisch Centrum, Universitair Ziekenhuis (UZ) Brussel, Vrije Universiteit Brussel (VUB), Brussels, Belgium., De Couck M; Department of Public Health, Mental Health and Wellbeing Research Group, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.; Faculty of Health Care, University College Odisee, Aalst, Belgium., Laoui D; Myeloid Cell Immunology Lab, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., De Grève J; Laboratory of Medical and Molecular Oncology (LMMO), Department of Medical Oncology, Oncologisch Centrum, Universitair Ziekenhuis (UZ) Brussel, Vrije Universiteit Brussel (VUB), Brussels, Belgium., De Ridder M; Department of Radiotherapy, Oncology Centre University Hospital Brussels (Universitair Ziekenhuis (UZ) Brussel), Brussels, Belgium., Gidron Y; Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel., Goyvaerts C; Laboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit Brussel, Brussels, Belgium.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Dec 01; Vol. 12, pp. 772555. Date of Electronic Publication: 2021 Dec 01 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.772555
Abstrakt:	The combination of radiotherapy (RT) with immunotherapy represents a promising treatment modality for non-small cell lung cancer (NSCLC) patients. As only a minority of patients shows a persistent response today, a spacious optimization window remains to be explored. Previously we showed that fractionated RT can induce a local immunosuppressive profile. Based on the evolving concept of an immunomodulatory role for vagal nerve stimulation (VNS), we tested its therapeutic and immunological effects alone and in combination with fractionated RT in a preclinical-translational study. Lewis lung carcinoma-bearing C57Bl/6 mice were treated with VNS, fractionated RT or the combination while a patient cohort with locally advanced NSCLC receiving concurrent radiochemotherapy (ccRTCT) was enrolled in a clinical trial to receive either sham or effective VNS daily during their 6 weeks of ccRTCT treatment. Preclinically, VNS alone or with RT showed no therapeutic effect yet VNS alone significantly enhanced the activation profile of intratumoral CD8 + T cells by upregulating their IFN-γ and CD137 expression. In the periphery, VNS reduced the RT-mediated rise of splenic, but not blood-derived, regulatory T cells (Treg) and monocytes. In accordance, the serological levels of protumoral CXCL5 next to two Treg-attracting chemokines CCL1 and CCL22 were reduced upon VNS monotherapy. In line with our preclinical findings on the lack of immunological changes in blood circulating immune cells upon VNS, immune monitoring of the peripheral blood of VNS treated NSCLC patients (n=7) did not show any significant changes compared to ccRTCT alone. As our preclinical data do suggest that VNS intensifies the stimulatory profile of the tumor infiltrated CD8 + T cells, this favors further research into non-invasive VNS to optimize current response rates to RT-immunotherapy in lung cancer patients. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Reijmen, De Mey, Van Damme, De Ridder, Gevaert, De Blay, Bouwens, Collen, Decoster, De Couck, Laoui, De Grève, De Ridder, Gidron and Goyvaerts.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu