CC BY-NC-ND 4.0 · Laryngorhinootologie 2021; 100(S 02): S100-S101
DOI: 10.1055/s-0041-1727893
Abstracts
Head-Neck-Oncology

“Hot” vs. “cold” tumors: Detecting differences in the inflamed vs. non-inflamed tumor microenvironment (TME) of head and neck squamous cell carcinoma (HNSCC) using single cell RNA sequencing

Cornelius H. L. Kürten
1   Universitätsklinikum Essen, Klinik für Hals-Nasen und Ohrenheilkunde, Essen
,
A Kulkarni
2   University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, United States
,
L Vujanovic
2   University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, United States
,
X Chen
4   University of Pittsburgh, Deparment of Biomedical Informatics, Pittsburgh, United States
,
U Duvvuri
5   University of Pittsburgh, Department of Otolaryngology, Pittsburgh, United States
,
S Kim
5   University of Pittsburgh, Department of Otolaryngology, Pittsburgh, United States
,
X Lu
4   University of Pittsburgh, Deparment of Biomedical Informatics, Pittsburgh, United States
,
AR. Cillo
3   University of Pittsburgh, Department of Immunology, Pittsburgh, United States
,
S Lang
1   Universitätsklinikum Essen, Klinik für Hals-Nasen und Ohrenheilkunde, Essen
,
RL. Ferris
5   University of Pittsburgh, Department of Otolaryngology, Pittsburgh, United States
› Author Affiliations
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    Introduction One mechanism of resistance to effective immunotherapy contributing to low response rates of 15-20 %  is the exclusion of immune cells from the tumor microenvironment (TME). A better biological understanding of this mechanism could have therapeutic consequences. Therefore, we explore differences in transcriptomic states of CD8+ T cells and tumor cells in between inflamed and non-inflamed HNSCC tumors.

    Methods Blood and tumor specimen from 18 treatment-na HNSCC patients were processed and run on the 10x Genomics 3’ single cell (V2) platform. Data aggregation and normalization were performed using CellRanger. The data was visualized using scanpy. Immune infiltration was calculated using an all-component total immune score using H&E staining (low, medium and high).

    Results Clustering analysis showed 34 different cell clusters (22 immune, 12 non-immune). A comparison of low vs. high infiltrated TME using gene set enrichment analysis in CD8+ T cells showed an increase in IFN? response, IFNa responses, and allograft rejection-associated gene sets. In CD8+ T cells from non-inflamed tumors TNFalpha signaling, UV-response, apoptosis, and hypoxia were upregulated. When comparing cancer cells, the inflamed showed an upregulation of epithelial–mesenchymal transition, MYC target genes and mitotic spindle formation, while in the non-inflamed, there was an upregulation of P53 pathway, fatty acid metabolism and glycolysis genes.

    Conclusions Transcriptomics can be used to analyze qualitative differences in inflamed vs non-inflamed HNSCC TME. This showed the cytotoxic T cells from an infiltrated TME to have a pro-inflammatory transcriptome. Implications of this finding for treatment response will be explored in future studies.

    Poster-PDF A-1261.pdf

    Programmzur Internen Forschungsförderung Essen (IFORES)


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    Conflict of interest

    Der Erstautor gibt keinen Interessenskonflikt an.

    Address for correspondence

    Ferris Robert L.
    University of Pittsburgh, Department of Immunology
    Pittsburgh
    United States   

    Publication History

    Article published online:
    13 May 2021

    © 2021. 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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