Secretome and immune cell attraction analysis of head and neck cancers

• Published in: Cancer Immunology, Immunotherapy : CII Vol. 73; no. 11; p. 229
• Main Authors: Muijlwijk, Tara, Wondergem, Niels E., Ekhlas, Fatima, Remkes, Naomi, Nijenhuis, Dennis N. L. M., Fritz, Lennart, Ganzevles, Sonja H., Miedema, Iris H. C., Leemans, C. René, Poell, Jos B., Brakenhoff, Ruud H., van de Ven, Rieneke
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 09.09.2024; Springer Nature B.V
• Subjects: Antitumor activity; Cancer Research; Cancer-Associated Fibroblasts - immunology; Cancer-Associated Fibroblasts - metabolism; Cell adhesion & migration; Cell migration; Cell Movement; Chemokines; Chemokines - metabolism; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Fibroblasts; Head & neck cancer; Head and neck carcinoma; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Humans; Immune checkpoint inhibitors; Immunity; Immunity (Disease); Immunology; Lymphocytes T; Medicine; Medicine & Public Health; Metastases; Oncology; PD-1 protein; Secretome; Secretome - metabolism; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - immunology; Squamous Cell Carcinoma of Head and Neck - metabolism; Squamous Cell Carcinoma of Head and Neck - pathology; Tumor microenvironment; Tumor Microenvironment - immunology; Tumors; Cancer-associated fibroblasts; Head and neck squamous cell carcinoma; Tumor secretome; Dendritic cells; Chemokines; Immune cell attraction
• ISSN: 1432-0851; 0340-7004; 1432-0851
• DOI: 10.1007/s00262-024-03809-z

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.