J Gynecol Oncol.  2020 Mar;31(2):e19. 10.3802/jgo.2020.31.e19.

Significance of PD-L1 expression in carbon-ion radiotherapy for uterine cervical adeno/adenosquamous carcinoma

• Iijima M
• Okonogi N
• Nakajima N
• Morokoshi
• Kanda H
• Yamada T
• Kobayashi
• Banno K
• Wakatsuki
• Yamada S
• Kamada T
• Aoki D
• Hasegawa S

• KMID: 2470870
• DOI: http://doi.org/10.3802/jgo.2020.31.e19

Abstract

OBJECTIVE
Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT).
METHODS
The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes.
RESULTS
The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS.
CONCLUSION
CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.

Keyword

B7-H1 Antigen; Disease-free Survival; Heavy Ion Radiotherapy; Treatment Outcome; Uterine Cervical Neoplasms

MeSH Terms

Antigens, CD274
Biopsy
Carcinoma, Squamous Cell
Disease-Free Survival
Flow Cytometry
Heavy Ion Radiotherapy
Humans
Radiotherapy*
Treatment Outcome
Uterine Cervical Neoplasms
Antigens, CD274