Abstract 1528: Characterization of the tumor microenvironment of key suppressive myeloid populations in 11 commonly used preclinical syngeneic cancer models
Authors: Ringgaard Lars , Christensen Esben , Kristensen Lotte K. , Stavnsbjerg Camilla , Kjaer Andreas , Hansen Anders E. , Andresen Thomas L. 
Published: August 2019

The tumor microenvironment (TME) composition is a critical parameter for therapeutic outcome in cancer patients. Understanding the TME composition and influence on anti-cancer therapies is a valuable tool for developing new treatments. High TME infiltration of activated tumor specific cytotoxic T-cells (cT) and central memory T-cells is crucial for improved prognosis. Conversely, interpreting infiltration of innate myeloid populations is more complex due to their plasticity and overlapping phenotypes. Myeloid derived suppressor cells (MDSC) potently inhibit cT function and proliferation in the tumor. Especially monocytic MDSCs (Mo-MDSCs) are associated with poor prognosis due to high secretion of arginase, suppressive cytokine production, and ROS-induction. Patrolling monocytes (pMos) have recently gained interest due to their regulatory function and high phagocytic capacity. Both Mo-MDSCs and pMos are progenitors to tumor-associated macrophages (TAMs), which either activate or suppress cT function. Myeloid subsets are the most prevalent infiltrating populations in both human and murine tumors and additional research is needed to provide rational selection when choosing preclinical models. In the present study, we characterized the infiltration of key myeloid subsets and activation markers in 11 commonly used syngeneic tumor models with subcutaneous tumors between 100-500 mm3. Populations of interest included; polymorphonuclear-MDSCs (PMN-MDSCs/G-MDSCs), Mo-MDSCs, TAMs, pMos, and classical dendritic cells type 1. Furthermore, we characterized key activation/regulatory markers CD80, CD86, CD163, CD206, MHCII, arginase-1, PD1, and PD-L1 to elucidate how the expression of these varies across cancer models and populations. The presented work provides a valuable tool to researcher across all categories of anti-cancer therapies by providing optimal grounds for model selection in the preclinical setting.

Cell lineOriginDominant infiltrating immune population (% of viable cells)ASB-XIVPulmonary squamous cell carcinomacT (5.3%)CT26Colorectal carcinomapMo (7.1%)A20B cell lymphomaMo-MDSC (3.7%)MC38Colorectal adenocarcinomaTAM (31.4%)EG-7.OVAThymomaMo-MDSC (7.4%)SA1NFibrosacromapMo (17.6%)B16F10MelanomaMo-MDSC (3.1%)LL/2lung carcinomaMo-MDSC (17.9%)RENCARenal adenocarcinomapMo (9.2%)4T1Ductal breast carcinomaPMN-MDSC (17%)J558MyelomaVery low immune infiltration

Citation Format: Lars Ringgaard, Esben Christensen, Lotte K. Kristensen, Camilla Stavnsbjerg, Andreas Kjaer, Anders E. Hansen, Thomas L. Andresen. Characterization of the tumor microenvironment of key suppressive myeloid populations in 11 commonly used preclinical syngeneic cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1528.