Abstract 2530: Macrophage biomarkers CD68 and CD163 correlate with CRC patient survival
Authors: Miller Dannah , Hieber Kate , Paces Will , Nguyen Huong , Beharry Adam , Gianani Roberto 
Published: June 2022

Abstract
Background: Immune cells within the tumor microenvironment (TME) play a vital role in regulating tumor progression. Therefore, immunotherapies that elicit anti-tumor responses are of great interest for the treatment of various cancers. Macrophages are a current immune cell type of interest due to the ability to polarize into anti-tumor (M1) and pro-tumor (M2) phenotypes. The density and phenotype of macrophages within the tumor and TME have been linked to prognosis in multiple types of solid tumors. Our hypothesis is that colorectal cancer (CRC) patients with high immune infiltration and greater amounts of anti-tumor immune cells within the tumor compartment will have an increased time of survival compared to cancers with immune excluded or desert environments.
Methods: One CRC tumor microarray (TMA) containing primary tumors, metastases, and normal tissue were stained via multiplex immunofluorescence (mIF) for 6 different immune markers: CD3, CD8, CD56, CD68, CD163, and PD-L1. The stained TMAs were analyzed utilizing Flagship Biosciences’ proprietary image analysis platform. Machine learning algorithms used cellular features to stratify cells as belonging to either the tumoral or stromal compartment. Core level expression data was pulled and represented on a whole-cohort basis. All staining and image analysis outputs were reviewed by a board-certified, MD pathologist. Kaplan-Meier curves were generated using survival data in relation to the low, medium, and high expression of CD68, CD163, and/or PDL1 in the whole tissue, as well as tumor and stromal compartments. Patients were also stratified into low (1 and 2) and high (3 and 4) cancer stages.
Results: There is a correlation between patient survival and the presence or absence of macrophage markers CD68 and CD163 and lack of immune-suppressive marker PDL1. Specifically, lower levels of CD68+CD163- cells within the tumor compartment correlate with an increase in patient survival. Similarly, lower PDL1 expression in the stromal compartment positively correlate with prolonged patient survival in CRC patients.
Conclusion: Data generated through Flagship Biosciences’ image analysis platform showed a strong relationship between CD68 and CD163 presence and localization with CRC patient survival. Altering the immune cells within the tumor to an anti-tumor immune environment could increase patient survival times in high stage CRC patient populations. Combining immune checkpoint inhibitors with current FDA approved therapies for CRC are of interest to further extend patient survival, as PDL1 expression negatively correlate with CRC patient survival. Further, utilizing Flagship Biosciences’ image analysis software to understand cancer immune microenvironments should be further utilized to aid in diagnosis and treatment decisions.
Citation Format: Dannah Miller, Kate Hieber, Will Paces, Huong Nguyen, Adam Beharry, Roberto Gianani. Macrophage biomarkers CD68 and CD163 correlate with CRC patient survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2530.