Data from: Development of an adrenocortical cancer humanized mouse model to characterize anti-PD1 effects on tumor microenvironment
| Main Authors: | Lang, Julie, Capasso, Anna, Jordan, Kimberly R., French, Jena D., Kar, Adwitiya, Bagby, Stacey, M., Barbee, Jacob, Yacob, Betelehem W., Head, Lia S., Tompkins, Kenneth D., Freed, Brian M., Somerset, Hilary, Clark, Toshimasa J., Pitts, Todd M., Messersmith, Well A., Eckhardt, S. Gail, Wierman, Margaret E., Leong, Stephen, Kiseljak-Vassiliades, Katja |
|---|---|
| Format: | info dataset eJournal |
| Terbitan: |
, 2020
|
| Subjects: | |
| Online Access: |
https://zenodo.org/record/3998252 |
Daftar Isi:
- Context: While the development of immune checkpoint inhibitors has transformed treatment strategies of several human malignancies, research models to study immunotherapy in ACC are lacking. Objective: To explore the effect of anti-PD1 immunotherapy on the alteration of the immune milieu in ACC in a newly generated preclinical model and correlate with the response of the matched patient. Design, Setting and Intervention: To characterize the CU-ACC2-M2B patient-derived xenograft in a humanized mouse model, evaluate the effect of a PD-1 inhibitor therapy and compare to the CU-ACC2 patient with metastatic disease. Results: Characterization of the CU-ACC2-hu-CB-BRGS model confirmed ACC origin and match with the original human tumor. Treatment of the mice with pembrolizumab demonstrated significant tumor growth inhibition (TGI = 60%) compared to controls, which correlated with increased tumor infiltrating lymphocyte activity, with an increase of human CD8+ T cells (p<0.05), HLA-DR+ T cells (p<0.05) as well as Granzyme B+ CD8+ T cells (<0.001). In parallel, treatment of the CU-ACC2 patient, who had progressive disease, demonstrated a partial response with 79%-100% reduction in the size of target lesions, and no new sites of metastasis. Pre-treatment analysis of the patient's metastatic liver lesion demonstrated abundant intra-tumoral CD8+ T cells by immunohistochemistry. Conclusions: Our study reports the first humanized ACC PDX mouse model which may be useful to define mechanisms and biomarkers of response and resistance to immune-based therapies, to ultimately provide more personalized care for patients with ACC.
- Supplementary figuresJCEM-2019-00297 Supplementary figs.pdf