Abstract 1654: Myeloid-dominated spontaneous tumor models as the tool for the evaluation of immune modulators

Abstract BACKGROUND:Myeloid cells, such as TAMs and MDSCs and their correlation with solid tumor progression have been widely recognized. As researchers are turning their interests to explore myeloid related tumor models, spontaneous tumor models, which represent a natural development/progression of tumor under certain immune microenvironment, would be a valuable tool for such studies. Some traditional targeted drugs have been re-evaluated for their immune effects, for example, CDK inhibitors can trigger anti-tumor immunity beyond its cell cycle regulation. Methods:In prior studies we have identified two myeloid-dominant spontaneous tumor models, APCmin and MMTV-PyMT, which represented a myeloid-enriched(especially for gMDSCs) and low T cell infiltrated microenvironment compared to the congenic mice. Immune modulators including checkpoint inhibitors (aCTLA-4),NSAID (Celecoxib) and CDK4/6 inhibitor(Palbociclib) were applied to evaluate their efficacy to the two models and their influences on the immune microenvironment. RESULTS:As a result, CDK inhibitor Palbociclib showed a better curative effect on MMTV-PyMT model compared to aCTLA-4. It seems when aCTLA-4 only up-regulated T cell level, CDK inhibitor can both increase the tumor infiltrating T cells as well as decrease Treg and myeloid, which explain its good response on this myeloid-dominated model. In APCmin model, Celecoxib reduce adenomas and alleviate the anemia symptoms with its significant immune benefit: the increase of lymphocyte infiltration and the reversal of myeloid cell elevation. SUMMARY:In summary, APCmin and MMTV-PyMT can be used as good tool models for the evaluation of myeloid-related immune modulators. Citation Format: Xianzhi Zhai, Yuying Yang, Haoxia Zhao, Jingjing Jiang, Xuzhen Tang, Qunsheng Ji. Myeloid-dominated spontaneous tumor models as the tool for the evaluation of immune modulators [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1654.