CC BY-NC-ND 4.0 · Laryngorhinootologie 2019; 98(S 02): S256
DOI: 10.1055/s-0039-1685963
Poster
Oncology

Head and neck squamous cell carcinoma demonstrate heterogeneity in response to pembrolizumab and cetuximab ex vivo

M Berszin
1   HNO- Universitätsklinik Leipzig, Leipzig
,
I Michaelides
1   HNO- Universitätsklinik Leipzig, Leipzig
,
M Kolb
1   HNO- Universitätsklinik Leipzig, Leipzig
,
A Dietz
1   HNO- Universitätsklinik Leipzig, Leipzig
,
S Wiegand
1   HNO- Universitätsklinik Leipzig, Leipzig
,
G Wichmann
2   HNO-Universitätsklinik Leipzig, Leipzig
› Author Affiliations
 

Introduction:

Blockade of the immune checkpoint PD-1 with pembrolizumab (Pemb) is effective in a subgroup of head and neck squamous cell carcinoma (HNSCC). Open question is whether a combination of Pemb and a targeted therapy e.g. simultaneous targeting of the epidermal growth factor-receptor (EGFR) by cetuximab (E) will increase Pemb efficacy. We analyzed the colony formation of epithelial cells (CFec) in a short-time chemo-response test (FLAVINO).

Methods:

Collagenase-IV digested samples of 48 histopathologic confirmed HNSCC were seeded into laminin-coated 96-well plates. Pemb, E or PembE were added in at least quadruplicates adjusting to nominal concentrations of either 50 µg/ml Pemb, 50 µg/ml E or 50+50 µg/ml PembE. Cell culture supernatants were harvested after 3 days, adherent cells ethanol-fixed and CFec stained with FITC-labeled pan-cytokeratin antibodies.

Results:

21 HNSCC had CFec≥4/well in controls. Mean effects on CFec on laminin revealed suppression by Pemb, E and PembE. At the individual level a more heterogeneous outcome was noticed: CFec was significantly suppressed by Pemb, E and PembE in 3 (14%), 6 (28%) and 7 (33%) HNSCC. CFec, however, was found being significantly increased in 3 (14%), 1 (5%), and 2 (10%; 1/3 with increased CFec in sole Pemb, 1 with increased CFec in sole E) of 21 HNSCC. The in 4 HNSCC additively suppressed CFec but in 4 HNSCC observed stimulating effects demonstrate huge heterogeneity in response of HNSCC to PD-1 and also to combined PD-1/EGFR blockade.

Conclusion:

Combined PD-1/EGFR targeting by PembE is mostly able to increase suppressive Pemb effects on CFec. Potential adverse Pemb effects in about 20% of HNSCC may be detected by the FLAVINO assay.



Publication History

Publication Date:
23 April 2019 (online)

© 2019. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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