American Association for Cancer Research
10780432ccr201523-sup-241793_3_supp_6533864_qftylx.pdf (78.35 kB)

Supplementary Figure 1 from PD1 Blockade Enhances ICAM1-Directed CAR T Therapeutic Efficacy in Advanced Thyroid Cancer

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journal contribution
posted on 2023-03-31, 22:01 authored by Katherine D. Gray, Jaclyn E. McCloskey, Yogindra Vedvyas, Olivia R. Kalloo, Steve El Eshaky, Yanping Yang, Enda Shevlin, Marjan Zaman, Timothy M. Ullmann, Heng Liang, Dessislava Stefanova, Paul J. Christos, Theresa Scognamiglio, Andrew B. Tassler, Rasa Zarnegar, Thomas J. Fahey, Moonsoo M. Jin, Irene M. Min

Expression of ICAM1 and PD-L1 in anaplastic thyroid tumor cell lines.


American Thyroid Association

New York State Department of Health

Cancer Research Fund


Translational Research, Clinical & Translational Science Center



Advanced thyroid cancers, including poorly differentiated and anaplastic thyroid cancer (ATC), are lethal malignancies with limited treatment options. The majority of patients with ATC have responded poorly to programmed death 1 (PD1) blockade in early clinical trials. There is a need to explore new treatment options. We examined the expression of PD-L1 (a ligand of PD1) and intercellular adhesion molecule 1 (ICAM1) in thyroid tumors and ATC cell lines, and investigated the PD1 expression level in peripheral T cells of patients with thyroid cancer. Next, we studied the tumor-targeting efficacy and T-cell dynamics of monotherapy and combination treatments of ICAM1-targeting chimeric antigen receptor (CAR) T cells and anti-PD1 antibody in a xenograft model of ATC. Advanced thyroid cancers were associated with increased expression of both ICAM1 and PD-L1 in tumors, and elevated PD1 expression in CD8+ T cells of circulating blood. The expression of ICAM1 and PD-L1 in ATC lines was regulated by the IFNγ–JAK2 signaling pathway. ICAM1-targeted CAR T cells, produced from either healthy donor or patient T cells, in combination with PD1 blockade demonstrated an improved ability to eradicate ICAM1-expressing target tumor cells compared with CAR T treatment alone. PD1 blockade facilitated clearance of PD-L1 high tumor colonies and curtailed excessive CAR T expansion, resulting in rapid tumor clearance and prolonged survival in a mouse model. Targeting two IFNγ-inducible, tumor-associated antigens—ICAM1 and PD-L1—in a complementary manner might be an effective treatment strategy to control advanced thyroid cancers in vivo.