Clin Cancer Res: PD1 blocking enhances the effectiveness of IAM1-targeted CAR T cells in the treatment of advanced thyroid cancer.

BACKGROUND: Advanced thyroid cancer, including low-differentiation and interdessional thyroid cancer (ATC), is a deadly malignancies with limited treatment options.
in early clinical trials, most ATC patients had an adverse reaction to programmed death 1 (PD1) closure.
need to explore new treatment options.
method: Gray and others detected the expression level of PD-L1 and intercellular adhesion molecule 1 (ICAM1) in thyroid tumors and ATC cell lineage, and detected the expression level of PD1 in the outer blood T cells of patients with thyroid cancer.
addition, the tumor targeting effect and T-cell dynamics of ICM1 targeted CAR T cells and anti-PD1 antibody mono-use and joint therapy were studied in the ATC heterogeneous graft model.
: Late thyroid cancer was associated with increased expression of ICAM1 and PD-L1 in tumors and PD1 expression of CD8-plus T cells in circulating blood.
expressions of ICAM1 and PD-L1 in ATC cell lines are regulated by the IFNg-JAK2 signaling path.
ICAM1-Targeted CAR T-Cell Joint PD1 blocked by healthy feeders or patient T-cells blocks the elimination of IAM1 expressive target tumor cells with stronger activity than single-use CAR T cells.
in mouse models, PD1 blocking promotes the removal of PD-L1 high tumor cloning and inhibits over-amplification of CAR-T, thus rapidly removing tumors and prolonging survival.
: Targeting IFNg induction, tumor-related antigens-ICAM1 and PD-L1 may be effective treatment strategies for controlling advanced thyroid cancer in a complementary manner.
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