Pattern recognition receptors’ and chemokine receptor expression on tonsil dendritic cells

Abstract: Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide and its high mortality rate highlights the necessity of developing novel therapies. Among the different cancer therapy methods, one of the most encouraging ones is dendritic cell (DC)-targeting immunotherapy, where desired antigens are delivered to DCs via antibodies. In this study, we investigated the frequency of CD123+ plasmacytoid DCs, CD1c+ myeloid DCs, CD141+ myeloid DCs and CD141-CD1c- myeloid DCs, in benign and malignant tonsils as well as in malignant nasopharyngeal tissue. We also assessed frequency of the DC subsets expressing CD206, CD207, CLEC9a, DEC205, Dectin-2, TLR-2, TLR-4, XCR1, Dectin-1 and CLECSF14 in benign and malignant tonsils in order to identify candidate receptors as therapeutic targets. Our results showed higher accumulation of DCs in malignant tonsils as compared to benign tonsils. Additionally, an almost 4-fold elevated CD11c myeloid DC/CD123 plasmacytoid DCs ratio was observed in malignant tonsils as compared to the corresponding ratio in benign tonsils. Further, CD123+ plasmacytoid DCs (out of DCs) were found in lower frequency in malignant tonsils as compared to the corresponding subset frequency in benign tonsils, whereas CD141-CD1c- myeloid DCs were more frequent in malignant tonsils compared to benign tonsils. Regarding marker expression on the different subsets, DEC205 and CD207 were expressed by a more considerable proportion of malignant tonsil resident DC subsets in comparison to other pathogen recognition receptors while the frequency of DC subsets expressing CD206, XCR1, Dectin-1 and CLECSF14 was relatively low. CLEC9a, Dectin-2, TLR2 and TLR4 were negligibly expressed. In addition, a significant increase in the frequency of CD1c+CD207+ myeloid DCs compared to CD123+CD207+ plasmacytoid DCs was found in benign tonsils as well as malignant tonsils. Also, the frequency of CD141-CD1c- myeloid DCs expressing XCR1 was higher in malignant tonsils as compared to benign tonsils. Furthermore, although low in frequency, CD141+XCR1+ myeloid DCs were also detected which could be of importance due to these DCs’ excellent ability at cross-presenting tumor antigens. In conclusion, as CD207, DEC205, CD206, Dectin-1, CLECSF14 and XCR1 were shown to be expressed by DC subsets and these receptors are known to be capable of inducing CD4 as well as CD8 T cell responses, we suggest that these receptors, in presence of appropriate costimulatory signals and adjuvants, could be suitable targets for DC-based immunotherapy of malignant tonsils.