Article Text

Download PDFPDF

1453 In-vivo tumor implantation site exhibits differential immune response in solid tumors
  1. Rajeev Shrimali,
  2. Sherry Liu,
  3. Jasmine Borroel,
  4. Carmen Suncio,
  5. Kristen Buck,
  6. Javier Rodriguez,
  7. Long Do,
  8. Warren Andrews,
  9. Yuan-Hung Chien,
  10. Bianca Carapia,
  11. Bridget Corcoran,
  12. Jantzen Sperry and
  13. Jonathan Nakashima
  1. Certis Oncology Solutions, San Diego, CA, USA


Background Emerging evidence highlights the importance of the local tumor microenvironment (TME) in evaluating the efficacy of new therapeutics, especially for immunotherapies. Historically, patient-derived xenograft (PDX) modeling involves subcutaneous implantation which minimally represents the actual human tumor site, as opposed to orthotopic implantation (O-PDX) which more accurately reflects the local TME. In this study, we sought to determine the immunological and functional differences between subcutaneous and orthotopic modeling.

Methods We implanted PDX models subcutaneously and orthotopically and performed gene set enrichment analysis (GSEA) on tumors to determine the differences in gene expression influenced by the TME. Furthermore, we developed peripheral blood mononuclear cell (PBMC) humanized PDX models to demonstrate differences in overall immune response and pharmacological outcome between the two implant settings.

Results GSEA revealed several significant pathways altered between subcutaneous and orthotopic tumors, including immunoregulatory interactions. PBMC humanized mice also showed differences in tumor infiltrating lymphocytes (TILs) as well as differential in vivo efficacy and immunophenotypes when challenged with checkpoint inhibition.

Conclusions We observed biological, immunological, and pharmacological differences between subcutaneous and orthotopic implantation of the same PDX model, highlighting the importance of study design when testing new therapies for greater translation into clinical success.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.