Abstract 2813: Clinical impact of immune microenvironment according to intratumoral locations of esophageal squamous cell carcinoma
Authors: Hatogai Ken , Fujii Satoshi , Kojima Takashi , Kitano Shigehisa , Daiko Hiroyuki , Yoshino Takayuki , Ohtsu Atsushi , Doi Toshihiko , Ochicai Atsushi 
Published: August 2019

Abstract
Background: The immune microenvironment is thought to differ according to the intratumoral location of esophageal squamous cell carcinomas (ESCCs), depending on cancer genomics and environmental factors. The aim of this study was to clarify the clinical impact of the immune microenvironment in different intratumoral locations in patients with ESCC.
Methods: The expressions of CD8 and PD-1 on tumor-infiltrating immune cells (TIICs) and the expression of PD-L1 on tumor cells (PD-L1TC) were immunohistochemically examined in the surface area (Surf), the center area (Cent), and the invasive front area (Inv) of tumors that had been surgically resected at our institution from 192 patients with ESCC. The expressions of each of the molecules were compared, and the relationships between the expressions of each of the molecules and overall survival (OS) were investigated for each of the three intratumoral locations.
Results: The median numbers of CD8+ TIICs were 132/mm2 in Surf, 118/mm2 in Cent, and 122/mm2 in Inv, while those of PD-1+ TIICs were 98/mm2 in Surf, 96/mm2 in Cent, and 92/mm2 in Inv, with no significant differences between each of the intratumoral locations for either type of TIICs. In addition, the number of TIICs was moderately to highly correlated between each intratumoral location for both CD8 (correlation coefficients [ρ] were 0.682 [Surf/Cent], 0.758 [Cent/Inv], and 0.669 [Inv/Surf]) and PD-1 (ρ were 0.617 [Surf/Cent], 0.753 [Cent/Inv], and 0.611 [Inv/Surf]). In contrast, the PD-L1 positive rate was 14.6% in Surf, 18.2% in Cent, and 12.0% in Inv, showing a significantly low positive rate in Inv compared with that in Cent (P = 0.012). Among patients with higher CD8+ TIICs, the PD-L1 positive rate was lower in Inv (22.1%) than that in Surf (26.3%) and Cent (29.2%), and it was also lower in Inv (21.1%) than that in Surf (27.4%) and Cent (25.5%) among patients with higher PD-1+ TIICs, with no significant differences. A high number of CD8+ TIICs and PD-1+ TIICs and PD-L1TC positivity were significantly related to a better OS in Surf and Cent, but not in Inv (CD8: stage-adjusted hazard ratio [HR] = 0.602 [P = 0.012, logrank] in Surf, HR = 0.649 [P = 0.018] in Cent, HR = 0.806 [P = 0.165] in Inv; PD-1: HR = 0.637 [P = 0.028] in Surf, HR = 0.645 [P = 0.021] in Cent, HR = 0.815 [P = 0.208] in Inv; PD-L1: HR = 0.442 [P = 0.044] in Surf, HR = 0.509 [P = 0.026] in Cent, HR = 0.778 [P = 0.718] in Inv). Among the 43 patients with PD-L1TC positivity in at least one intratumoral location, 20 patients with positive PD-L1TCin Surf and/or Cent but not in Inv demonstrated a strong tendency toward a better OS than the 23 patients with PD-L1TC positivity in Inv (HR = 0.339 [P = 0.053]).
Conclusions: Despite the homogeneous distribution of TIICs, PD-L1 expression and the relationship between the immune microenvironment and OS differed according to the intratumoral location of ESCC. The immune microenvironments in Surf and Cent have a clinical impact.
Citation Format: Ken Hatogai, Satoshi Fujii, Takashi Kojima, Shigehisa Kitano, Hiroyuki Daiko, Takayuki Yoshino, Atsushi Ohtsu, Toshihiko Doi, Atsushi Ochicai. Clinical impact of immune microenvironment according to intratumoral locations of esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2813.