High expression of PD-L1 on conventional dendritic cells in tumour-draining lymph nodes is associated with poor prognosis in oral cancer

Author:

Eric Hjalmarsson,Piersiala Krzysztof,Lagebro Vilma,Farrajota Neves Da Silva Pedro,Petro Marianne,Starkhammar Magnus,Elliot Alexandra,Bark Rusana,Margolin Gregori,Kumlien Georén Susanna,Cardell Lars-Olaf

Abstract

Abstract Introduction Oral squamous cell carcinoma (OSCC), while common and with a favorable prognosis in early stages, presents a marked reduction in survival rate upon metastasis to lymph nodes. Early detection of lymph node metastasis via biomarkers could enhance the therapeutic strategy for OSCC. Here, we explored dendritic cells (DCs) and cytotoxic T-cells in tumour-draining lymph nodes (TDLNs) as potential biomarkers. Method Dendritic cells and cytotoxic T-cells in 33 lymph nodes were analyzed with multi-parameter flow cytometry in TDLNs, regional non-TDLNs surgically excised from 12 OSCC patients, and compared to 9 lymph nodes from patients with benign conditions. Results Our results displayed a higher proportion of conventional cDC1s with immunosuppressive features in TDLN. Further, high PD-L1 expression on cDC1 in TDLNs was associated with metastasis and/or recurrent disease risk. Also, elevated levels of memory CD8+ T-cells and terminally exhausted PD-1+TCF-1CD8+ T-cells were observed in TDLNs and non-TDLNs compared to healthy lymph nodes. Conclusions We conclude that TDLNs contain cells that could trigger an anti-tumor adaptive response, as evidenced by activated cDC1s and progenitor-like TCF-1+ T-cells. The detection of high PDL1 expression on cDC1s was indicative of TDLN metastasis and an adverse prognosis, proposing that PD-L1 on dendritic cells in TDLN could serve as a predictive biomarker of OSCC patients with a worse prognosis.

Funder

Radiumhemmets Forskningsfonder

Cancerfonden

Center for Innovative Medicine

Karolinska Institute

Publisher

Springer Science and Business Media LLC

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