Data from: Development of an adrenocortical cancer humanized mouse model to characterize anti-PD1 effects on tumor microenvironment

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.