Abstract 1281: Transfer of a PDX biobank in a humanized setting to enable immune-oncology studies
Authors: Eva Oswald, Lea Gröhne, Dorothee Lenhard, Loreen Weichert, Julia B. Schueler
Journal: Cancer Research (2025)

Abstract The field of cancer immunology is rapidly moving towards immunomodulatory therapeutic strategies, including multi-specific antibodies, immune checkpoint inhibition, as well as potential vaccination strategies. Consequently, large biobanks of patient-derived tumor xenografts (PDX) models can serve as powerful tools. While one well-known major drawback of the PDX platform is the lack of an immunological competent host, the implantation of PDX models in humanized mice compensates for this. The focus of this project was to evaluate subcutaneous implanted PDX models of different tumor types in human immune system (HIS) reconstituted mice for presence of human immune cells. We determined the immune cell infiltration of more than 30 PDX models across different tumor types. PDX were implanted subcutaneous in 1-3 HIS mice per PDX, including models of lung, colon, breast and kidney cancer. Flow cytometry (FC) and immunohistochemistry (IHC) was performed to determine and characterize tumor infiltrating lymphocytes (TIL) in tumor tissue and human immune cells in hematopoietic organs of the mice. In addition, the expression of different surface markers related to immune-oncology pathways such as PDL-1 was determined by IHC in the tumor tissue. Overall, we confirmed good engraftment in the hematopoietic organs of the tumor bearing animals ranging from 40% - 80% in peripheral blood, spleen and bone marrow. The engraftment rate was not influence by the respective PDX model nor the donor of the CD34+ cells used for humanization. In contrast, the TIL rate was variable across the analyzed tumor panel and mainly driven by the tumor model ranging from 0.13% - 45% CD45+ cells. Tumors with a TIL rate &amp;gt;5% were defined as hot vs the cold tumors with a TIL rate &amp;lt; 5%. Up to now, there is no clear pattern of tumor types or molecular subtypes being specifically hot or cold. However, in the group of renal cancer an increased number of hot tumors was determined. The comparison with donor patient samples displayed a high correlation between TIL rate of donor patient tissue and PDX, emphasizing the tumor model as the main driver for this feature. The expression of PDL-1 was influenced by the presence of human immune cells: PDL1 expression was more than threefold upregulated in hot tumors, whereas it was downregulated in cold tumors although this effect was less pronounced. In continuation of the current study, we will examine more PDX models and expand the characterization to the corresponding tumoroids to provide in vitro and in vivo platforms that can robustly translate preclinical results of immunomodulatory drug testing into the clinic. Citation Format: Eva Oswald, Lea Gröhne, Dorothee Lenhard, Loreen Weichert, Julia B. Schueler. Transfer of a PDX biobank in a humanized setting to enable immune-oncology studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1281.