Abstract

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 non-small cell lung carcinoma (NSCLC) 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 immune desert environments. Methods: One NSCLC 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 based on survival data in relation to the low, medium, and high expression of CD68 and/or CD163 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. Specifically, lower levels of CD68+CD163- cells within the tumor and stroma compartments correlate with an increase in patient survival. There is also a correlation of a high level of expression of CD163+, CD68+CD163-, or CD68+CD163+ cells with increased patient survival in high stage patients compared to low stage patients. Specifically in high stage NSCLC patients, a higher level of CD163+ expression correlates with a reduced lifespan compared to patients with medium and low expression. Conclusion: Data generated through Flagship Biosciences’ image analysis platform showed a strong relationship between immune cell presence and localization with NSCLC patient survival. Altering the immune cells within the tumor to an anti-tumor immune environment could increase patient survival times. 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 NSCLC 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 1720.

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