Abstract 4317: Prognostic significance of SIRPa+ macrophages in esophageal squamous cell carcinoma
Authors: Li Yida , Chu Li , Yang Xi , Chu Xiao , Ni Jianjiao , Zhu Zhengfei 
Published: September 2020

Abstract
While the immune checkpoint blockade has revolutionized the cancer treatment with potent and durable anti-tumor immunity, the benefits remained limited in many occasions, highlighting the needs for predictive biomarkers and improved patient stratification strategies. Here, we aimed to evaluate the clinical relevance of inhibitory receptor signal regulatory protein alpha (SIRPα), predominantly expressed in macrophages in patients with esophageal squamous cell carcinoma (ESCC). For this purpose, tissue microarrays (TMA) were constructed, comprising a total of 249 ESCC patients who underwent radical surgery in 2013. Macrophages associated in situ immune contexture were deciphered by quantitative multiplex fluorescence immunohistochemistry (mFIHC) using Vectra3™ multispectral imaging platform and digital pathology workstation (HALO™). CD68+ macrophages were identified with or without co-expression of SIRPα and PDL1, while tumor cells (CK+) found with differential expressed inhibitory CD47 and PDL1. A comprehensive profiling including density, percentage and spatial/neighborhood association of all the subsets was performed and correlated for prognostic significance.
The univariate and multivariate analysis showed that pT, pN stage, tumor length, macrophage density, ratio of SIRPα+ macrophages to total macrophages (rSIRPα), PDL1+ tumor cell density appeared as independent prognostic factors. Log-rank test showed that more infiltration of macrophages had a better overall survival (OS) (P=.004). Lower rSIRPα instead of the density of SIRPα+ macrophages could predict a better OS (P=.027). These indicate that the survival of ESCC patient could be significantly influenced by both the density and the status of macrophages. Furthermore, rSIRPα and PDL1+ cell density was used to stratify patients with similar state of innate or adaptive immunity. Within the subgroup of SIRPαloPDL1hi patients, patients with lower number of SIRPα + macrophages in a radius of 60µm of CD47+ tumor cell (SIRPα60µm) had a significantly better OS (P=.030) while in the subgroup of rSIRPαlo patients, lymph node metastasis was more frequent and broader in patients with higher CD47+ tumor cell density (P=.041).
In conclusion, this study revealed the clinical significance of the density and location of SIRPα+ macrophages in ESCC. We found that higher rSIRPα indicated a worse survival. Moreover, within the subgroup of rSIRPαloPDL1hi patients, higher SIRPα60µm indicated a worse survival. These findings highlighted a differential immune paradigm direct the prognostic trajectories and must not be ignored for patients with therapeutic resistance. Along with the correlation between CD47+ tumor cells and metastasis, we spotted high heterogeneity among ESCC patients and therefore suggesting more filtered stratification according to immune network for personalized treatment selection to predict robust anti-tumor immune response.
Citation Format: Yida Li, Li Chu, Xi, Yang, Xiao Chu, Jianjiao Ni, Zhengfei Zhu. Prognostic significance of SIRPa+ macrophages in esophageal squamous cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4317.