肿瘤细胞治疗研究
英文原题：Systemically inducing trained immunity overcomes solid tumors' immunosuppressive microenvironment.
Systemically inducing trained immunity overcomes solid tumors' immunosuppressive microenvironment.
我们的数据表明，训练免疫的系统性诱导能够重新平衡免疫系统，从而实现有效的检查点阻断治疗。
造血祖细胞在癌症免疫抑制中的起源作用日益受到关注。我们此前已表明，利用纳米药物诱导训练免疫可增强检查点阻断疗法。在此，我们研究了该方法诱导的训练免疫如何系统性克服免疫抑制性肿瘤微环境。我们在黑色素瘤小鼠模型中发现，肿瘤微环境的变化反映了造血系统的功能性变化。单细胞测序方法揭示，肿瘤相关巨噬细胞群体从免疫抑制性向抗肿瘤性转变。独特的是，训练免疫与检查点阻断联合治疗动员了NK 细胞，这些细胞与髓系细胞区室的功能性变化协同作用，有效激活了T细胞。最后，我们在乳腺癌、肺癌和胰腺癌小鼠模型中确立了该方法的有效性。总体而言，我们的数据表明，系统性诱导训练免疫可重新平衡免疫系统，从而实现有效的检查点阻断疗法。
Hematopoietic bone marrow progenitors are increasingly implicated as an origin of immunosuppression in cancer. We have previously shown that trained immunity induction using nanomedicine potentiates checkpoint blockade therapy. Here, we studied how this approach's induction of trained immunity systemically overcomes the immunosuppressive tumor microenvironment. We found changes in the tumor microenvironment to mirror functional changes in the hematopoietic system in a melanoma mouse model. Single cell sequencing methods disclosed a shift in the tumor-associated macrophage population from immunosuppressive to antitumorigenic. Uniquely, a trained immunity and checkpoint blockade combination therapy mobilized natural killer cells which, in conjunction with the functional changes in the myeloid cell compartment, effectively activated T cells. Last, we established the effectiveness of our approach in mouse models of breast, lung, and pancreatic cancer. Collectively, our data show that the systemic induction of trained immunity rebalances the immune system for effective checkpoint blockade therapy.
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