肿瘤细胞治疗研究
英文原题：Radiation enhances the efficacy of EGFR-targeted CAR-T cells against triple-negative breast cancer by activating NF-κB/Icam1 signaling.
这些结果表明，CAR-T 治疗联合放疗可能是三阴性乳腺癌（TNBC）治疗的一种有前景的策略。
三阴性乳腺癌（TNBC）是侵袭性最强的乳腺癌亚型，治疗选择有限。据报道，50%–75%的TNBC患者表达表皮生长因子受体（EGFR），使其成为有前景的癌症治疗靶点。我们显示，EGFR靶向嵌合抗原受体（CAR）T细胞联合放疗，在免疫功能完整和免疫缺陷的原位TNBC小鼠模型中均增强抗肿瘤疗效。有趣的是，联合治疗显著增加了肿瘤浸润CAR-T细胞数量。联合疗效不依赖肿瘤放射敏感性，也不依赖淋巴细胞清除预处理。细胞因子分析显示，联合治疗未增加细胞因子释放综合征（CRS）风险。RNA测序分析显示，EGFR靶向CAR-T联合放疗增加了肿瘤内CD8+ T细胞和自然杀伤（NK）细胞浸润。机制上，放疗通过激活核因子κB（NF-κB）信号，显著上调TNBC细胞ICAM1表达，进而促进CAR-T细胞浸润和杀伤。结果提示，CAR-T细胞联合放疗可能是治疗TNBC的有前景策略。
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, with limited treatment options. Epidermal growth factor receptor (EGFR) is reported to be expressed in 50%-75% of TNBC patients, making it a promising target for cancer treatment. Here we show that EGFR-targeted chimeric antigen receptor (CAR) T cell therapy combined with radiotherapy provides enhanced antitumor efficacy in immunocompetent and immunodeficient orthotopic TNBC mice. Intriguingly, this combination therapy resulted in a substantial increase in the number of tumor-infiltrating CAR-T cells. The efficacy of this combination was independent of tumor radiosensitivity and lymphodepleting preconditioning. Cytokine profiling showed that this combination did not increase the risk of cytokine release syndrome (CRS). RNA sequencing (RNA-seq) analysis revealed that EGFR-targeting CAR-T therapy combined with radiotherapy increased the infiltration of CD8 + T and natural killer (NK) cells into tumors. Mechanistically, radiation significantly increased Icam1 expression on TNBC cells via activating nuclear factor B (NF- B) signaling, thereby promoting CAR-T cell infiltration and killing. These results suggest that CAR-T therapy combined with radiotherapy may be a promising strategy for TNBC treatment.
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