Abstract 5949: Modulate TAM infiltration at cancer-immune interface by targeting at monocyte migration

Extensive infiltration of tumor-associated macrophages (TAMs) into the solid tumor microenvironment (TME), where they promote angiogenesis, initiate metastasis, and tune immunosuppression, has long been proven to correlate with worse patient prognosis. Thus, much significance has been attached on either impeding TAM infiltration or reversing pro-tumoral TAMs back into phagocytic M1 phenotype. Nevertheless, while revealing underlying mechanisms of blocking TAM recruitment, widely adopted in vitro migration assays like Transwell, µ-slides fail to distinguish cell’s random migration from chemotaxis (biased migration) and introduce 3D extracellular matrix environment. Here we present data that monocytes, as major replenishment source of TAMs, massively boost their random migration via paracrine pathway to initiate early-stage infiltration using an advanced 3D multi-compartment organoid model. In addition, before re-educated into TAMs, monocytes in the TME are capable of inducing triple negative breast cancer cells’ hyper-proliferation by activating their MEK/ERK signaling pathway. This work provides evidence that TAM infiltration is driven by monocytes’ random/biased migration separately and identifies a potential combinational immunotherapy targeting at monocytes instead of TAMs. Citation Format: Wenxuan Du, Adrian Johnston, Praful Nair, Jingyi Zhu, Khin Sandar Win, Bryan Zhou, Jude Phillip, Pei-Hsun Wu, Denis Wirtz. Modulate TAM infiltration at cancer-immune interface by targeting at monocyte migration. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5949.