Secretome and immune cell attraction analysis of head and neck cancers.
Cancer-associated fibroblasts
Chemokines
Dendritic cells
Head and neck squamous cell carcinoma
Immune cell attraction
Tumor secretome
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
09 Sep 2024
09 Sep 2024
Historique:
received:
14
05
2024
accepted:
12
08
2024
medline:
9
9
2024
pubmed:
9
9
2024
entrez:
9
9
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39249543
doi: 10.1007/s00262-024-03809-z
pii: 10.1007/s00262-024-03809-z
doi:
Substances chimiques
Chemokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
229Subventions
Organisme : Cancer Center Amsterdam (CCA)
ID : PV 19/02
Informations de copyright
© 2024. The Author(s).
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