Data from: Development of an adrenocortical cancer humanized mouse model to characterize anti-PD1 effects on tumor microenvironment
Creators
- 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
Description
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.
Notes
Files
JCEM-2019-00297 Supplementary figs.pdf
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