Abstract 2953: Tumor-associated macrophages infiltration highly associated with PD-L1 expression in gastric cancer

Abstract

Abstract Objectives: programmed death ligand 1 (PD-L1) is key protein for tumor to acquire the evacuation form T cell immune response and PD-L1 inhibitors are useful for an immune checkpoint blockade therapy. Tumor-associated macrophages (TAM) facilitate not only tumor cell progression, but also immunosuppression, which prevent tumor cell attack by T cell. Therefore, TAM is considered to be associated with PD-L1 expression, however it remain unclear in gastric cancer (GC). Methods: We performed immunohistochemical staining of PD-L1, CD68 (pan-macrophage) and CD163 (M2 macrophage) in 217 GC sample tissue microarray. The area of CD68 and CD163 positive cells were evaluated by using by the Cytoplasmic V2.0 algorithm on the Aperio ImageScope software. Results: 31 samples (14.3%) were positive for PD-L1 expression. The mean of rate for CD68 and CD163 positive area were 6.8±0.38% and 6.2±0.30%, respectively. CD163 positive macrophage infiltration is significantly more in diffuse type tumor than in intestinal type tumor (diffuse (n=111): 6.9%, intestinal (n=91): 5.3%, p=0.0056), but CD68 positive macrophage infiltration is similar in both type (p=0.38). Interestingly, PD-L1 expression tumor have significantly more CD68 and CD163 positive macrophage infiltration (CD68: PD-L1 negative 6.3%, positive 10.4%, p=0.0002, CD163: PD-L1 negative 5.7%, positive 9.2%, p<0.0001). PD-L1 expression and CD68 and CD163 positive area had no relationship between any clinicopathological features. Conclusions: Macrophages infiltration in GC is highly associated with PD-L1 expression of tumor cells. M2 macrophage infiltration is significantly associated with diffused type of GAC. This result suggests that TAM infiltration is associated with the immunosuppression through upregulating PD-L1 expression in GC cells. Thus, macrophages infiltration can serve as a potential therapeutic target. . Citation Format: Kazuto Harada, Jeannelyn S Estrella, Arlene M Correa, Lang Ma, Xiaoquan Dong, Yan Xu, Wayne L Hofstette, Kazuki Sudo, Hisashi Onodera, Koyu Suzuki, Akihiro Suzuki, Randy L Johnson, Zhenning Zhenning, Shumei Song, Jaffer A Ajani, Hisashi Onodera. Tumor-associated macrophages infiltration highly associated with PD-L1 expression in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2953. doi:10.1158/1538-7445.AM2017-2953