Intratumoral plasmid IL-12 expands CD8+ T cells and induces a CXCR3 signature in triple-negative breast tumors that sensitizes patient to anti-PD-1 therapy. Intratumoral plasmid IL-12 expands CD8+ T cells and induces a CXCR3 signature in triple-negative breast tumors that sensitizes patient to anti-PD-1 therapy

We show that plasmid IL-12 injected intratumorally followed by co-localized electroporation induces a CXCR3 gene signature with enhanced antigen presentation, expansion, and licensing of T cells systemically. We highlight a patient that was previously non-responsive to atezolizumab and nab-paclitaxel, who demonstrated significant clinical response to nivolumab following TAVOTM therapy. Overall design: CD45+ cells were sorted from treated murine TNBC tumors following treatment with control or IL-12 plasmid. Cells from 3 mice were pooled from each treatment and scRNAseq was performed. Gene expression and TCR libraries were created using 10x Genomics Chromium Single Cell 5’ Library Construction Kit (v1.1).

本研究证实，瘤内注射白细胞介素12（IL-12）质粒后辅以共定位电穿孔，可诱导产生CXCR3基因特征谱，并系统性增强T细胞的抗原呈递、扩增与活化许可。本研究还报道了1例既往对阿替利珠单抗（atezolizumab）与白蛋白结合型紫杉醇无应答的患者，其在接受TAVOTM治疗后，对纳武利尤单抗（nivolumab）展现出显著的临床应答。
总体实验设计：从经对照质粒或IL-12质粒处理的小鼠三阴性乳腺癌（TNBC）瘤组织中分选CD45+细胞；每组处理的3只小鼠的细胞混合后进行单细胞RNA测序（scRNAseq）；基因表达与T细胞受体（TCR）文库采用10x基因组学（10x Genomics）Chromium单细胞5’文库构建试剂盒（v1.1）构建。