Abstract

Radiotherapy (RT) has an established role in the treatment of patients with non-small-cell lung cancer (NSCLC). Unfortunately, tumor irradiation upregulates the expression of various inflammatory cytokines which contribute to radioresistance with subsequent tumor progression and metastasis. Emerging evidence suggests that myeloid-derived suppressor cells (MDSC) play a key role in this response as they contribute to an immunosuppressive tumor microenvironment (TME) and tumor relapse after irradiation. Recent studies indicate that the vagal nerve is an immunomodulator and that its stimulation (VNS) can inhibit the inflammatory process through the so-called ‘cholinergic anti-inflammatory pathway’. Moreover, an experimental murine study demonstrated that the efferent vagal pathway is an important suppressor of MDSC expansion in colorectal cancer.
This study tends to investigate if non-invasive VNS could suppress RT-induced tumor promoting inflammation and revert the immunosuppressive TME in lung cancer.
Methods Preclinically, lung tumor-bearing C57Bl/6 mice were treated with VNS alone, fractionated RT (2.4 Gy, 4 consecutive days) plus VNS (2x/day, 25HZ, 5 consecutive days) or RT plus sham VNS. Tumor volumes were monitored via bioluminescent imaging. In addition, murine spleens and lungs were subjected to immunological analysis via flow cytometry. Furthermore, NSCLC patients (n=6) were enrolled in a blind randomized clinical trial. Patients were subjected to VNS (2x/day, 20Hz) or sham (control arm) in combination with conventional chemo-RT. Blood was collected in both setups before, during and at the end of treatment for further flow cytometry-based analysis and ELISA.
Preliminary data show that the orthotopic lung cancer model allows evaluation of therapeutic RT efficacy. Furthermore, we observed immune modulation upon VNS, more specifically an increase in conventional type 2 dendritic cells. Accordingly, clinical results show VNS-mediated upregulation of dendritic cells, natural killer cells and CD8+ T cells in blood. In contrast both the granulocytic and monocytic MDSC populations decreased over time.
Though most results are preliminary, we observe trends towards the amelioration of antitumor immunity with reduction of tumor promoting MDSC. VNS is a safe and non-invasive treatment option, therefore it could have a positive impact on (immune)therapy strategies for a broad range of cancer patients.

Original languageEnglish
Publication statusPublished - 7 Feb 2020
EventBACR Annual Meeting 2020: Cancer metastasis: From bedside to bench - Vrije Universiteit Brussel, Campus Jette, Brussels, Belgium
Duration: 7 Feb 20207 Feb 2020
Conference number: 26th
https://www.bacr.be/program/

Conference

ConferenceBACR Annual Meeting 2020
CountryBelgium
CityBrussels
Period7/02/207/02/20
Internet address

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