Comprehensive immunohistochemical analysis of tumor microenvironment immune status in esophageal squamous cell carcinoma.
Immunotherapy with anti-PD-1 antibody preliminarily showed promising efficacy for treating esophageal squamous cell carcinoma (ESCC). Herein, we used tissue microarrays and immunohistochemically analyzed PD-L1 and various tumor infiltrating immune cells (TIICs) in specimens from 196 ESCC patients who had undergone curative resection without preoperative therapy. PD-L1 expressions in tumor cells (TCs) and TIICs, as well as infiltration of lymphocytes (CD4+, CD8+, FOXP3+, and PD- 1+) and macrophages (CD68+ and CD204+), were evaluated. PD-L1 was expressed in TCs of 18.4% and in TIICs of 83.3% of these patients. PD-L1 expressions in TCs and TIICs were associated with significant infiltration of various TIIC types, especially CD8+ cells. PD-L1 expressions in both TCs and TIICs were significantly associated with favorable overall survival, and combining their levels enhanced prognostic accuracy. Prognostic impacts of PD-L1 expressions in TCs and TIICs, abundant PD-1+ cell infiltration, a high CD8+/FOXP3+ ratio, and the CD8+/CD204+ ratio remained significant after adjusting for clinicopathological factors. In conclusion, PD-L1 expression reflects anti-tumor immunity, and PD-1/PD-L1 expression and the ratio of infiltrating effector to immune suppressor cells have prognostic value. Therapeutic strategies inhibiting the PD-1/PD-L1 signal and immune suppressor cells are anticipated in ESCC patients.
Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.|Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.|Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
Ken
K
Hatogai
Department of Experimental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Tokyo, Japan.
Shigehisa
S
Kitano
Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
Satoshi
S
Fujii
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Takashi
T
Kojima
Department of Esophageal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Hiroyuki
H
Daiko
Biostatistics Division, Center for Research Administration and Support, National Cancer Center, Kashiwa, Japan.
Shogo
S
Nomura
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Takayuki
T
Yoshino
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.|Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.
Atsushi
A
Ohtsu
Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
Yuichi
Y
Takiguchi
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Toshihiko
T
Doi
Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
Atsushi
A
Ochiai
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000096:biosynthesis / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000276:immunology* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis / Q000276:immunology; D016019:Survival Analysis; D059016:Tumor Microenvironment / Q000276:immunology*
D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
PD-L1; esophageal cancer; immunohistochemistry; macrophage; tumor infiltrating lymphocyte