Prognostic effect of programmed cell death ligand 1/programmed cell death 1 expression in cancer stem cells of human oral squamous cell carcinoma

Todoroki,Keita; Abe,Yushi; Matsuo,Katsuhisa; Nomura,Hidetoshi; Kawahara,Akihiko; Nakamura,Yoshiaki; Nakamura,Moriyoshi; Seki,Naoko; Kusukawa,Jingo

doi:10.3892/ol.2024.14213

Prognostic effect of programmed cell death ligand 1/programmed cell death 1 expression in cancer stem cells of human oral squamous cell carcinoma

Authors:
- Keita Todoroki
- Yushi Abe
- Katsuhisa Matsuo
- Hidetoshi Nomura
- Akihiko Kawahara
- Yoshiaki Nakamura
- Moriyoshi Nakamura
- Naoko Seki
- Jingo Kusukawa
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Affiliations: Dental and Oral Medical Center, Kurume University, School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Fukuoka 830‑0011, Japan, Department of Dentistry and Oral Surgery, Oita Saiseikai Hita Hospital, Hita, Oita 877‑1292, Japan
Published online on: January 4, 2024 https://doi.org/10.3892/ol.2024.14213
Article Number: 79
Copyright: © Todoroki et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The relationship between cancer stem cells (CSCs) in oral squamous cell carcinoma (OSCC) and programmed cell death ligand 1 (PD‑L1)/programmed cell death 1 (PD‑1) remains unclear. Therefore, the present study aimed to clarify the association between the CD44v3^high/CD24^low immunophenotype of CSCs in OSCC and PD‑L1/PD‑1 co‑expression, and to assess the prognostic effect of CSCs in terms of immune checkpoint molecules. Formalin‑fixed, paraffin‑embedded tissue samples and clinicopathological data from 168 patients with OSCC were retrospectively retrieved. Immunohistochemical staining and reverse transcription quantitative polymerase chain reaction were applied to a tissue microarray of the invasive front of each case. Semi‑automated cell counting was used to assess CD44v3, CD24, PD‑L1 and PD‑1 expression by immunohistochemistry (IHC) using a digital image analysis program. Associations between immunological markers and clinicopathological variables were estimated. Patients with the CSC immunophenotype CD44v3^high/CD24^low, and patients with a high PD‑L1/PD‑1‑positive cell density in the tumor parenchyma and stroma had significantly lower survival rates. Furthermore, patients with the CSC immunophenotype (CD44v3^high/CD24^low) and high PD‑L1/PD‑1 co‑expression had even lower survival rates (P<0.01, log‑rank test). Notably, there was a positive correlation between CD44v3 and PD‑L1 expression (τ=0.1096, P=0.0366, Kendall rank correlation coefficient) and a negative correlation between CD24 and PD‑1 expression (τ=‑0.1387, P=0.0089, Kendall rank correlation coefficient). Additionally, the high CD44v3 expression group, as determined by IHC, exhibited significantly decreased expression of U2 small nuclear RNA auxiliary factor 1 (U2AF1) at the mRNA level compared with that in the low CD44v3 expression group (P<0.001, Mann‑Whitney U test), and U2AF1 and PD‑L1 mRNA expression exhibited a significant negative correlation (τ=‑0.3948, P<0.001, Kendall rank correlation coefficient). In conclusion, CSCs in OSCC may evade host immune mechanisms and maintain CSC stemness via PD‑L1/PD‑1 co‑expression, resulting in unfavorable clinical outcomes.

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