Abstract 3144: Pleiotrophin drives a pro-metastatic immune niche within breast tumor microenvironment

Abstract Immune cells in the tumor microenvironment (TME) can impact cancer cell invasion, seeding and colonization of secondary metastatic sites. Our findings show that Pleiotrophin (PTN), a unique and previously under-studied heparin binding cytokine, contributes to inflammation within the TME. PTN appears to be particularly efficient in recruiting neutrophils, which have been reported to cause immune suppression. Consequently, inhibition of PTN pharmacologically or genetically results in lower breast cancer metastasis to lungs and better survival in multiple mouse models of breast cancer. Corroborating our mouse studies, we have found that higher PTN expression in breast cancer patient plasma correlates with poor prognosis. Concurrently, stage IV breast cancer patients that have lower PTN expression have a highly significant survival advantage (median survival 78.27 months) over patients expressing high levels of PTN (median survival 27.5 months). Additionally, we have also found PTN positive cancer cells are enriched in metastatic lesions suggesting that PTN-high cancer cells are more successful at colonizing and surviving at the secondary site. Uncovering the function of PTN in these unique cancer cells might have a major impact in the clinical setting. Overall, our data suggests that PTN is important in driving a pro-metastatic immune niche within the TME that promotes tumor cell escape from the primary tumor and survival of metastatic cancer cells in secondary sites. Additionally, our studies highlight that inhibition of PTN has potential to reduce metastatic burden in breast cancer and suggest that future studies testing the combination of PTN inhibition with standard chemotherapy or immune therapy are warranted. Citation Format: Debolina Ganguly, Tuong V. Ngo, Morgan Coleman, Noah Sorrelle, Adrian Dominguez, Jason Toombs, Marcel Schmidt, Fa V. Mora, David G. Ortega, Anton Wellstein, Rolf A. Brekken. Pleiotrophin drives a pro-metastatic immune niche within breast tumor microenvironment [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 3144.