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Poster Display session

205P - Modelling of NSCLC aPD1 responses in bronchoscopic biopsies on chip (bronchoBOCs)

Date

31 Mar 2023

Session

Poster Display session

Presenters

Maria Matthaiakaki Panagiotaki

Citation

Journal of Thoracic Oncology (2023) 18 (4S): S149-S153.
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Authors

K. Douka1, M. Frantzi2, M. Matthaiakaki Panagiotaki3, F. Mazzoni4, S. Fancelli4, S. Pilozzi4, P. Ulivi5, L. Antonuzzo4, A. Delmonte6, V. Roman7, I. Sigala8, N. Gianniou8, I. Kalomenidis8, M. Makridakis9, A. Vlahou9, H. Mischak2, M. TSOUMAKIDOU10

Author affiliations

  • 1 Vari-Voula-Vouliagmeni/GR
  • 2 Mosaiques Diagnostics, Hannover/DE
  • 3 BSRC Alexander Fleming, Vari-Voula-Vouliagmeni/GR
  • 4 Careggi University Hospital (AOU – Careggi), Florence/IT
  • 5 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola/IT
  • 6 Scientific Institute of Romagna for the Study of Cancer (IRST), Meldola/IT
  • 7 Institute of Virology - Center of Immunology, Bucharest/RO
  • 8 1st Department of Critical Care and Pulmonary Medicine, University of Athens School of Medicine, Evaggelismos Hospital, Athens, Athens/GR
  • 9 Center of Systems Biology, Biomedical Research Foundation, Academy of Athens, Athens/GR
  • 10 BSRC Alexander Fleming, 16672 - Vari-Voula-Vouliagmeni/GR

Resources

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Abstract 205P

Background

Eligibility for aPD1 therapy is based on PD-L1 expression, but few patients experience durable responses. Tumours cultured in microfluidic devices (tumour-on-chip) recapitulate the in vivo microenvironment and are being developed as drug screening platforms. Their application to advanced NSCLC is hampered by the unavailability of surgical tumour resection specimens in these patients. To overcome this, we aimed to develop a methodological approach that will allow culture of bronchoscopic tumour biopsies on chips to model drug responses.

Methods

Bronchoscopic biopsies from 25 NSCLC patients were dissected and filtered to obtain tumour spheroids of 40–100 μm in size (3 × 105 spheroids/biopsy). AIM biotech chips consisting of a central channel and 2 lateral channels were used. Tumour spheroids were dispersed in matrigel and split in the central channels of 2 chips. Endothelial cells were cultured at the lateral channels to mimic vasculature. Pembrolizumab (aPD1) vs isotype control was administered in the lateral channels (10 μg/mL). After 48 h effluents were analysed by cytometric bead array (CBA) for cytokines and cytotoxic molecules. Spheroids, along with effluents, were analysed by mass spectrometry (LC MS/MS).

Results

CBA analysis showed a robust increase in the release of granzyme B and granulysin, used by T cytotoxic cells to kill cancer cells, in pembrolizumab-exposed effluents. LC MS/MS identified 122 differentially abundant proteins in pembrolizumab-treated vs control spheroids and 71 differentially abundant proteins in effluents. Pathway enrichment analysis suggested that pembrolizumab activated innate and adaptive immune responses and signal transduction pathways in bronchoBOCs.

Conclusions

We developed the first bronchoBOCs that develop physiologically-relevant responses to aPD1. We envisage to use bronchoBOCs for biomarker identification, as drug screening platform and to increase our mechanistic understanding of human tumour immunity.

Legal entity responsible for the study

B.S.R.C. Alexander Fleming.

Funding

ERA Per Med.

Disclosure

All authors have declared no conflicts of interest.

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