Abstract LB-A008: Reversing immune checkpoint inhibitor resistance rherapy in advanced thyroid cancer

作者：Joah E. Lee, Jaden Nguyen, Jarod Olay, Kyleigh Kimbrell, Amber Lu, Aime T. Franco, Alan L. Epstein, Trevor E. Angell, Melissa G. Lechner · 发表于：Cancer Immunology Research · 年份：2026 · DOI：10.1158/2326-6074.io2026-lb-a008 · 研究领域：Immune cells in cancer、Inflammation biomarkers and pathways、Thyroid Cancer Diagnosis and Treatment

Abstract Background: Patients with advanced thyroid cancer have few treatment options and poor survival [e.g. 10% at 10 years for radioactive iodine-refractory differentiated thyroid cancer (DTC)] and immune checkpoint inhibitors (ICI) have not shown benefit in these patients. The goal of this project is to identify novel strategies to improve the efficacy of ICI therapy in thyroid cancer. Prior work showed that suppressive myeloid cells are important contributors to immune escape and ICI resistance in thyroid cancer. In addition, clinical studies have shown that the presence of MDSCs in the peripheral blood of thyroid cancer patients correlates with more advanced disease and recurrence. In melanoma, colon, and lung tumor models, the TLR9 agonist CpG can act on myeloid cells to reduce suppressive function, increase antigen presentation and augment T cell proliferation, activation, and ingress into the tumor. We hypothesized that combined ICI therapy with TLR9 agonist CpG reverse of MDSC suppression to improve anti-tumor efficacy of ICI in DTC. Methods: Mice bearing poorly differentiated BRAFV600E+ papillary thyroid cancer tumors were randomized to treatment with isotype control or ICI (anti-PD1 or anti-PDL1; 250mg/dose i.p., 2x weekly) antibodies, with or without CpG-1826 peritumorally. In addition, we tested ICI with directly conjugated CpG given intraperitoneally compared to ICI alone as a potential systemic therapy. Immune populations in tumor and spleen were evaluated usi...