白血病复发是靶向CD19嵌合抗原受体T细胞（CART19）治疗失败的首要原因，而骨髓微环境对CAR-T细胞的抑制作用可能是CD19阳性复发关键环节。我们发现骨髓MSCs可显著抑制CART19细胞增殖及肿瘤杀伤，且通过分泌IDO发挥作用，而IDO抑制剂可逆转上述作用，其他研究小组结果则显示Kyn-AhR通路参与外源性IDO抑制CAR-T细胞功能，因此我们推测骨髓MSCs通过IDO-Kyn-AhR通路诱导急性淋巴细胞白血病（ALL）细胞逃逸CART19细胞肿瘤杀伤，导致疾病复发。本课题拟从动物、细胞和分子水平，阐明骨髓MSCs通过IDO-Kyn-AhR通路抑制CART19细胞肿瘤杀伤的作用及其分子机制，明确IDO抑制剂在逆转骨髓MSCs抑制CART19肿瘤杀伤中的作用，为阐明CAR-T治疗后CD19阳性复发的分子机制提供实验依据，为临床制定针对CD19阳性复发新的治疗策略奠定实验基础。

Leukemia relapse is the leading cause of treatment failure of anti-CD19 chimeric antigen receptor T cells (CART19), and the suppression of CAR-T cells by bone marrow microenvironment maybe play a key role in CD19 positive relapse. Our previous study showed that bone marrow microenvironment MSCs can inhibit the proliferation and tumor killing of CART19 cells by secreting IDO, IDO inhibitor can reverse the inhibition of CART19, other study showed that Kyn-AhR pathway may be involved in the suppression of CAR-T cells by exogenous IDO. Based on these results, we speculate that bone marrow microenvironment MSCs can induce ALL cells to escape the tumor killing of CART19 cells through IDO-Kyn-AhR pathway and lead to leukemia relapse. Our further study intends to elucidate the function and molecular mechanisms of the inhibition of CART19 tumor killing by bone marrow microenvironment MSCs through IDO-Kyn-AhR pathway, demonstrate the effect of IDO inhibitor in reversing the inhibition of CART19 tumor killing by MSCs. Our research will afford the experimental proof for clarify the mechanisms of CD19 positive relapse after CART19 therapy, provide the experimental basis for the clinical development of new intervention strategy.