PD-L1 expression is associated with senescence in HNSCC cells after irradiation

Introduction Fractionated irradiation (FR) can cause premature senescence of tumor cells. Interactions between senescence and the immune system are poorly understood to date. Therefore, our study addresses the detection of senescence-associated modulation of PD-L1 expression under FR in the HNSCC model.

Methods Established HNSCC cell lines (UM-SCC-11B, -14C and -22B) served as in vitro model system. The expression levels of phosphorylated, i.e. activated ERK (pERK) and PD-L1 were determined by Western blot after application of 5 x 2Gy. Using SA-ß-Gal staining and detection of p21CDKN1A and yH2AX by IHC/IF, postradiogenic induction of senescence was then assessed and verified in the 3D HNSCC model.

Results Upon irradiation, senescence-like subpopulations were observed in all cell lines, showing activation of PD-L1 and upregulation of established senescence markers p21 and γH2AX. SA-β-Gal-positive cells were found in all lines. The 3D model supported these results, with levels of pERK1/2, PD-L1, p21CDKN1A, and γH2AX varying among FR, reflecting the marked heterogeneity of HNSCC.

Discussion Fractionated irradiation can generate a subpopulation of HNSCC tumor cells characterized by senescence-typical cellular changes and marked expression of PD-L1. The data suggest a link between irradiation-induced activation of checkpoints and the occurrence of senescence in HNSCC. Irradiation treatment induces senescence in both 2D and 3D head and neck tumor models, possibly related to the regulation of PD-L1 expression.

Programm zur Förderung der Gleichstellung und Karriere von ärztinnen und Wissenschaftlerinnen an der Universitätsmedizin Mannheim

Publication History

Article published online:
12 May 2023