Research Papers:

Association between PD-L1 expression combined with tumor-infiltrating lymphocytes and the prognosis of patients with advanced hypopharyngeal squamous cell carcinoma

Takeharu Ono _, Koichi Azuma, Akihiko Kawahara, Tetsuro Sasada, Satoshi Hattori, Fumihiko Sato, Buichiro Shin, Shun-Ich Chitose, Jun Akiba and Umeno Hirohito

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Oncotarget. 2017; 8:92699-92714. https://doi.org/10.18632/oncotarget.21564

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Takeharu Ono1, Koichi Azuma2, Akihiko Kawahara3, Tetsuro Sasada4, Satoshi Hattori5, Fumihiko Sato1, Buichiro Shin1, Shun-Ich Chitose1, Jun Akiba3 and Umeno Hirohito1

1Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume, Japan

2Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan

3Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan

4Cancer Vaccine Center, Kanagawa Cancer Center Research Institute, Yokohama, Japan

5Biostatistics Center, Kurume University School of Medicine, Kurume, Japan

Correspondence to:

Takeharu Ono, email: [email protected]

Keywords: PD-L1, immunohistochemistry, hypopharyngeal squamous cell carcinoma, neoadjuvant chemotherapy, CD8+ TILs

Received: March 24, 2017     Accepted: September 05, 2017     Published: October 06, 2017


Limited information is available regarding the immune-related prognostic factors of patients with advanced hypopharyngeal squamous cell carcinoma (HPSCC). The expression of programmed cell death-ligand 1 (PD-L1) in tumor cells contributes to a mechanism that allows cancer cells to escape immune surveillance. We investigated whether PD-L1 or human leukocyte antigen (HLA) class I expression in tumor cells and the tumor-infiltrating lymphocyte (TIL) density were associated with the tumor response to neoadjuvant chemotherapy (NAC) and survival in patients with advanced HPSCC. We retrospectively reviewed 83 consecutive patients with stage III or IV HPSCC who received NAC. We evaluated PD-L1 and HLA class I expression and TIL density using immunohistochemistry. Univariate and multivariate analyses demonstrated that CD8+ TIL density was an independent and significant predictive factor for the response to NAC, progression-free survival (PFS) and overall survival (OS), whereas PD-L1 or HLA class I expression did not significantly correlate. The subgroup analysis revealed that a higher CD8+ TIL density without detectable PD-L1 expression tended to be associated with longer patient survival. These results suggest that PD-L1 expression levels combined with CD8+ TIL density may serve as a predictive biomarker for patients with stage III or IV HPSCC receiving NAC.

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