应用携带抗CD19嵌合抗原受体（CAR）的T细胞的移植免疫疗法是治疗晚期B细胞恶性肿瘤的一种新方法。然而，肿瘤异质性、细胞因子释放综合征（CRS）和CAR-T细胞衰竭使肿瘤的CAR-T细胞疗法具有挑战性。气阴三魄三良 (SLS) 方剂在肿瘤治疗中有显著疗效，并且与肿瘤免疫疗法结合可以提高临床疗效。然而，SLS与免疫疗法的体外或体内药效评估尚无，其潜在的免疫学机制仍不清楚。本研究的目标是确定 SLS 作为抗CD19 CAR-T细胞辅助治疗的效应和潜在机制。 通过高效液相色谱法（HPLC），检测到 SLS 中的42种成分。使用TCMSP数据库，分析了16种具有药理活性的成分。预测的靶标包括IL-2、IL-6、IL-10、TNF-α、CASP7和CASP9。体外研究显示，SLS 能剂量依赖性地促进未修饰T细胞和抗CD19 CAR-T细胞对Raji细胞系的杀伤作用。同时，SLS抑制未修饰T细胞和抗CD19 CAR-T细胞的衰竭，促进抗CD19 CAR-T细胞的增殖，降低IL-6、IL-10和TNF-α的水平，增加粒酶B的水平。体内研究显示，SLS有效提高了抗CD19 CAR-T细胞的抗肿瘤功能，延长了小鼠的生存时间，降低了IL-6、GM-CSF和IL-17的水平。随后的转录组分析显示，SLS抑制了T细胞的IL-17信号通路和凋亡信号通路。此外，SLS通过下调抗CD19 CAR-T细胞中的IL-17A、IL-6、TNF-α、GM-CSF、S100A8、CASP7、CASP9和CASP10的表达调节了IL-17信号通路和凋亡信号通路。SLS在改善B细胞淋巴瘤治疗中的抗CD19 CAR T细胞功能、增强这些细胞的杀伤能力、减少与炎症相关的潜在风险以及提供协同作用和减弱作用方面具有潜在的辅助作用。SLS的机制部分通过凋亡和IL-17信号通路实现（如IL-17A、IL-6、TNF-α、GM-CSF和粒酶B）。 版权所有 © 2023 by Elsevier B.V. 发表。

Adoptive T-cell therapy with anti-CD19 chimeric antigen receptor (CAR)-expressing T cells is a new approach for treating advanced B-cell malignancies. However, CAR-Tcell therapies for tumors are challenging due to tumor heterogeneity, cytokine release syndrome (CRS), and CAR-T cell exhaustion. The Qi Yin San Liang San (SLS) decoction has a significant curative effect in treating tumors and can improve clinical efficacy when combined with tumor immunotherapy. However, there has been no in vitro or in vivo pharmacodynamic evaluation of SLS in combination with immunotherapy, and the underlying immunological mechanism remains unclear.The study objective was to determine the auxiliary effect and potential mechanism of SLS as an adjuvant treatment with anti-CD19 CAR-T cells for B-cell lymphomas.Network pharmacology analyses, in vitro and in vivo studies, and transcriptome sequencing analyses were performed.Forty-two components were detected in SLS by HPLC. Sixteen pharmacologically active ingredients were analyzed by searching the TCMSP database. The predicted targets included IL-2, IL-6, IL-10, TNF-α, CASP7, and CASP9. In vitro studies revealed that SLS can dose-dependently promote the killing effect of unmodified T and anti-CD19 CAR-T cells against Raji cell lines. Meanwhile, SLS inhibited unmodified T and anti-CD19 CAR-T cell exhaustion, promoted anti-CD19 CAR-T cell proliferation, reduced the levels of IL-6, IL-10, and TNF-α, and increased granzyme B levels. In vivo studies, SLS effectively improved the anti-tumor function of anti-CD19 CAR-T cells, prolonged the survival of the mice, and reduced the levels of IL-6, GM-CSF, and IL-17. Subsequently, the transcriptomic analysis showed that SLS inhibited the IL-17 signaling pathway and the apoptosis signaling pathway of T cells. In addition, SLS downregulated the expression of IL-17A, IL-6, TNF-α, GM-CSF, S100A8, CASP 7, CASP 9, and CASP 10 in anti-CD19 CAR-T cells. SLS regulated the IL-17 signaling pathway and apoptosis signaling pathway in anti-CD19 CAR-T cells.SLS has a potential auxiliary role in enhancing the function of anti-CD19 CAR T cells in the treatment of B-cell lymphoma, improving the killing ability of these cells, reducing the potential risk associated with inflammation, and providing synergistic and attenuating effects. The mechanism of SLS is partially mediated by the apoptosis and IL-17 signaling pathways (such as IL-17A, IL-6, TNF-α, GM-CSF, and Granzyme B).Copyright © 2023. Published by Elsevier B.V.