Journal for immunotherapy of cancer
PTPN22 as a novel therapeutic target: a key intracellular checkpoint for NK cell therapy
Por Uong TNT, Yoon M, Nguyen NPNM y 5 más.
Contenido en inglés
Resumen
Background
PTPN22, a protein tyrosine phosphatase (PTP) family member, has recently emerged as an intracellular regulator in adaptive immune cells. However, its function in natural killer (NK) cells remains unclear despite its high expression in innate immune cells.
Methods
We analyzed single-cell RNA-sequencing (scRNA-seq) datasets and The Cancer Genome Atlas (TCGA) to evaluate PTPN22 expression in NK cells and its association with clinical outcomes. We established a CRISPR-mediated PTPN22 knockout platform for NK cell gene editing and evaluated PTPN22 function using both genetic deletion and pharmacological inhibition across multiple NK cell platforms. Cytotoxicity and cytokine production were assessed against hematologic and solid tumor targets, including CD19+ and mesothelin-positive (MSLN+) cancer cells. PTPN22 knockout (PTPN22KO) anti-CD19/CAR-NK92 cells were tested in Nalm6 xenograft models.