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...