Abstract 3878: Opposing CD68/CD163 tumour immune microenvironments revealed using a large multi-tumor tissue microarray (TMA) comprising cores from invasive margin (IM) and tumor center (TC)
Authors: Cumberbatch Marie , Kim Woo Ho , Memeo Lorenzo , Colarossi Lorenzo , Womack Christopher , Bhagat Milan 
Published: September 2020

Abstract
Macrophages contribute to cancer-associated inflammation, and those with M2-like phenotype have been reported to be involved in tumor progression, immunosuppression, metastasis and angiogenesis. CD163 is considered a marker of M2-like macrophages/monocytes and high expression has been associated with poor prognosis in various tumor indications. To investigate the relative contribution of macrophage/monocyte cell populations to the tumor immune microenvironment across multiple tumor types concurrently, we have utilised a multi-tumor tissue microarray (TMA) comprising 30 different tumor indications, with approximately 12 cases per tumor type, each case represented by duplicate 1mm cores (1 from IM and 1 from TC). Serial sections of TMA slides (n=5) were stained by immunohistochemistry for CD68 and CD163, and cells/mm2/core delivered by digital image analysis of scanned images (CellProfilerTM). Comparative analysis of all tumor types regardless of core location (IM and TC combined) revealed lung, renal and cervical cancers to be the most highly infiltrated with CD68+ macrophages, while the greatest CD163 staining was observed for sarcoma and glioblastoma (GBM). Interestingly, a direct comparison of multiple tumor types simultaneously as performed here has revealed strongly opposing immune microenvironments in different tumor indications with respect to the balance of expression of CD68 and CD163. Higher frequencies of CD68+ macrophages relative to low CD163 expression was observed for prostate, endometrial, renal, cervical, thyroid, pancreatic, hepatic, small bowel and urothelial cancers. Conversely, a strong M2-like milieu exhibiting CD163+ cell frequencies exceeding CD68+ macrophages numbers was apparent for sarcoma, GBM, mesothelioma, bladder, cutaneous squamous cell carcinoma, gastrointestinal stromal tumor, head and neck squamous cell carcinoma, ER+ and Her2+ breast cancers. The remaining tumors, including cholangiocarcinoma, triple negative breast, lung, ovarian, gallbladder, colorectal, gastric, and esophageal cancers, all exhibited equivalent levels of infiltrating CD68+ and CD163+ cells. Analyses of IM versus TC revealed further complexities of the tumor immune microenvironment. For some disease settings, divergent CD163:CD68 ratios were observed for IM versus TC, whereas for other indications the ratio remained unchanged. In conclusion, concurrent analysis of multiple tumor indications for CD68 and CD163 has revealed immunosuppressive M2-like macrophage/monocyte tumor immune microenvironments that vary markedly between tumor types and within some tumors. These data may help to identify those patients that may benefit from therapies that target this immune pathway.
Citation Format: Marie Cumberbatch, Woo Ho Kim, Lorenzo Memeo, Lorenzo Colarossi, Christopher Womack, Milan Bhagat. Opposing CD68/CD163 tumour immune microenvironments revealed using a large multi-tumor tissue microarray (TMA) comprising cores from invasive margin (IM) and tumor center (TC) [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 3878.