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Open Access 01-11-2024 | Research

Secretome and immune cell attraction analysis of head and neck cancers

Authors: Tara Muijlwijk, Niels E. Wondergem, Fatima Ekhlas, Naomi Remkes, Dennis N. L. M. Nijenhuis, Lennart Fritz, Sonja H. Ganzevles, Iris H. C. Miedema, C. René Leemans, Jos B. Poell, Ruud H. Brakenhoff, Rieneke van de Ven

Published in: Cancer Immunology, Immunotherapy | Issue 11/2024

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Abstract

Immune checkpoint inhibitors are approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) but the response rate is only 13–18%. For an effective antitumor immune response, trafficking of immune cells to the tumor microenvironment (TME) is essential. We aimed to better understand immune cell migration as well as the involved chemokines in HNSCC. A transwell assay was used to study immune cell migration toward TME-conditioned medium. While T cell migration was not observed, conventional dendritic cell (cDC) migration was induced by TME-conditioned media. cDC migration correlated with various proteins in the TME secretome. CCL8, CXCL5, CCL13 and CCL7 were tested in validation experiments and addition of these chemokines induced cDC migration. Using single cell RNA-sequencing, we observed expression of CCL8, CXCL5, CCL13 and CCL7 in cancer-associated fibroblasts (CAFs). Depleting fibroblasts led to reduced cDC migration. Thus CAFs, while often seen as suppressors of antitumor immunity, play a role in attracting cDCs toward the head and neck cancer TME, which might be crucial for effective antitumor immunity and response to therapies. Indeed, we found RNA expression signatures of the indicated chemokines, cDC and CAF subpopulations, to be significantly higher in baseline tumor specimen of patients with a major pathological response to pre-surgical anti-PD-1 treatment compared to non-responding patients.
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Metadata
Title
Secretome and immune cell attraction analysis of head and neck cancers
Authors
Tara Muijlwijk
Niels E. Wondergem
Fatima Ekhlas
Naomi Remkes
Dennis N. L. M. Nijenhuis
Lennart Fritz
Sonja H. Ganzevles
Iris H. C. Miedema
C. René Leemans
Jos B. Poell
Ruud H. Brakenhoff
Rieneke van de Ven
Publication date
01-11-2024
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 11/2024
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-024-03809-z

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