TY  - JOUR
AU  - Steen, Sonja
AU  - Semmelmayer, Karl
AU  - Flechtenmacher, Christa
AU  - Hoffmann, Jürgen
AU  - Freier, Kolja
AU  - Horn, Dominik
AU  - Hess, Jochen
AU  - Freudlsperger, Christian
AU  - Moratin, Julius
TI  - Dynamic Up-Regulation of PD-L1 in the Progression of Oral Squamous Cell Carcinoma.
JO  - International journal of molecular sciences
VL  - 24
IS  - 22
SN  - 1422-0067
CY  - Basel
PB  - Molecular Diversity Preservation International
M1  - DKFZ-2023-02492
SP  - 16386
PY  - 2023
AB  - The introduction of immune checkpoint inhibition for recurrent and metastatic head and neck cancer has brought a new treatment option for patients suffering from advanced oral cancers without a chance for curation using surgery or radiotherapy. The application of immune checkpoint inhibitors in most cases is based on the expression levels of PD-L1 in the tumor tissue. To date, there is a lack of data on the dynamic regulation of PD-L1 during disease progression. Therefore, this study aimed to evaluate the expression levels of PD-L1 in a large cohort of patients (n = 222) with oral squamous cell carcinoma including primary and recurrent tumors. Semiautomatic digital pathology scoring was used for the assessment of PD-L1 expression levels in primary and recurrent oral squamous cell carcinoma. Survival analysis was performed to evaluate the prognostic significance of the protein expression at different stages of the disease. We found a significant up-regulation of PD-L1 expression from primary disease to recurrent tumors (mean PD-L1 H-scores: primary tumors: 47.1 ± 31.4; recurrent tumors: 103.5 ± 62.8, p < 0.001). In several cases, a shift from low PD-L1 expression in primary tumors to high PD-L1 expression in recurrent tumors was identified. Multivariate Cox regression analysis did not reveal a significantly higher risk of death (p = 0.078) or recurrence (p = 0.926) in patients with higher PD-L1 expression. Our findings indicate that the exclusive analysis of primary tumor tissue prior to the application of checkpoint blockade may lead to the misjudgment of PD-L1 expression in recurrent tumors.
KW  - Humans
KW  - Squamous Cell Carcinoma of Head and Neck
KW  - Carcinoma, Squamous Cell: pathology
KW  - B7-H1 Antigen: metabolism
KW  - Up-Regulation
KW  - Mouth Neoplasms: genetics
KW  - Neoplasm Recurrence, Local: genetics
KW  - Head and Neck Neoplasms
KW  - HNSCC (Other)
KW  - PD-L1 (Other)
KW  - immune checkpoint inhibitor (Other)
KW  - metastases (Other)
KW  - oral cancer (Other)
KW  - recurrence (Other)
KW  - B7-H1 Antigen (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:38003576
C2  - pmc:PMC10671831
DO  - DOI:10.3390/ijms242216386
UR  - https://inrepo02.dkfz.de/record/285669
ER  -