Association between radiotherapy-induced alteration of programmed death ligand 1 and survival in patients with uterine cervical cancer undergoing preoperative radiotherapy

• Published in: Strahlentherapie und Onkologie 2020-08, Vol.196 (8), p.725-735
• Main Authors: Tsuchiya, Takaaki, Someya, Masanori, Takada, Yu, Hasegawa, Tomokazu, Kitagawa, Mio, Fukushima, Yuki, Gocho, Toshio, Hori, Masakazu, Nakata, Kensei, Hirohashi, Yoshihiko, Torigoe, Toshihiko, Saito, Tsuyoshi, Sakata, Koh-ichi
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigens; Antineoplastic Agents, Alkylating - therapeutic use; B7-H1 Antigen - analysis; Cancer; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - radiotherapy; Carcinoma, Squamous Cell - surgery; Carcinoma, Squamous Cell - therapy; CD8-Positive T-Lymphocytes - chemistry; CD8-Positive T-Lymphocytes - immunology; Cell death; Cervical cancer; Chemoradiotherapy, Adjuvant; Chemotherapy; Cisplatin - therapeutic use; Death; Female; Forkhead Transcription Factors - analysis; Gene Expression Regulation, Neoplastic - radiation effects; HLA Antigens - analysis; Humans; Immune system; Immunology; Infiltration; Kaplan-Meier Estimate; Leukocytes; Ligands; Lymphocytes; Lymphocytes, Tumor-Infiltrating - radiation effects; Medicine; Medicine & Public Health; Middle Aged; Neoadjuvant Therapy; Neoplasm Proteins - analysis; Oncology; Original Article; Prognosis; Proportional Hazards Models; Radiation therapy; Radiotherapy; Retrospective Studies; ROC Curve; Survival; T-Lymphocyte Subsets - chemistry; T-Lymphocyte Subsets - immunology; Treatment Outcome; Tumors; Uterine Neoplasms - immunology; Uterine Neoplasms - radiotherapy; Uterine Neoplasms - surgery; Uterine Neoplasms - therapy
• ISSN: 0179-7158; 1439-099X
• DOI: 10.1007/s00066-019-01571-1

Purpose To evaluate radiotherapy-induced changes in the expression of programmed death ligand 1 (PD-L1), programmed death 1 (PD-1), and human leukocyte antigen class I (HLA-1) in patients with uterine cervical cancer, as well as infiltration of CD8+ and Forkhead box P3+ (FoxP3+) T lymphocytes into tumor tissue and the prognostic value of these parameters. Materials and methods We performed immunohistochemical analysis of pre-radiotherapy biopsies and corresponding post-radiotherapy resected tissues in 104 uterine cervical cancer patients undergoing preoperative chemoradiotherapy or radiotherapy alone. We scored the expression of various proteins to distinguish positive from negative samples. Results PD-L1-expressing tumor cells (PD-L1 TC) increased significantly after chemoradiotherapy ( p  = 0.043). CD8+ T cell infiltration ( p  = 0.002) and FoxP3+ T cell infiltration ( p  = 0.003) decreased significantly after chemoradiotherapy. Expression of PD‑1, PD-L1-expressing immune cells (PD-L1 IC), and HLA‑1 did not change after chemoradiotherapy. In biopsy specimens obtained before chemoradiotherapy or radiotherapy, greater infiltration of CD8+ T cells ( p  = 0.001) and FoxP3+ T cells ( p  = 0.003) were significant predictors of better overall survival (OS). In surgical specimens obtained after chemoradiotherapy or radiotherapy, greater infiltration of PD-L1 TC was the only significant predictor of better OS ( p