Abstract 4570: Selective depletion of regulatory T cells suppressed neuroblastoma tumor growth in mice

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Abstract Purpose of the study Neuroblastoma (NB) is the most common solid extracranial tumor in childhood. Regulatory T cells (Treg) are known to have immune suppressive capacity and to be involved in tolerance establishment. As they support tumor growth and help some tumors to overcome recognition by the host, they are considered to be an important target. Treg are reportedly increased in blood of NB patients. However, there are no scientific proofs to date that they are involved in neuroblastoma growth. To address this important question we employed Foxp3-DTR mice to selectively deplete Treg upon orthotopic application of syngeneic neuroblastoma cells. Methods Orthotopic NB tumors were generated in mice Foxp3-DTR mice and in C57Bl/6J controls by subcapsular tumor cell injection of NB975A cells into the left kidney. Primary tumor growth was analysed for 23 days by high frequency ultrasound measurement. To deplete Treg, InjectionDepletion of Diphtheria Toxin (DT, 15 ng/g bodyweight) intraperitoneally every 4 days in Foxp3.DTR mice depleted the Treg pool. Control Foxp3.DTR animals received PBS and control C57B/l6 received DT. All mice were sacrificed 23 days after tumor inoculation. Tumor as wells as immune cells harvested from spleen and inguinal lymph nodes were analyzed by Flow Cytometry, Immunofluorescenceimmunohistochemistry and qRT-PCR. Results In control mice bearing tumors, Treg presence was confirmed at the contact zone between the kidney and the growing, inoculated tumor. Mice devoid of Treg (Foxp3-DTR+DT) showed a significantly reduced tumor growth compared to animals with normal Treg frequencies (Foxp3-DTR+PBS). Tumor growth in wild type controls was not affected by the application of DTR. Conclusion Ablation of Treg hindered the growth of NB, strongly suggesting their potential as therapeutic target for this aggressive childhood tumor. Citation Format: Sophie von Lenthe, Christine Weißenborn, Ana Claudia Zenclussen, Stefan Fest, Leonid Metelitsa. Selective depletion of regulatory T cells suppressed neuroblastoma tumor growth in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4570.