Anti-PD1/PDL1单药治疗在大多数实体肿瘤中未能获得足够理想的结果。间充质干细胞（MSC）据报道对某些肿瘤具有治疗效果，但是MSC在结直肠癌（CRC）中的功能需要进一步研究。本研究旨在探讨MSC在CRC中的治疗效果和其对抗αPD1抗体（αPD1）敏感性的改善，并评估可能的机制。在小鼠接受MSC和/或αPD1处理后，检测肿瘤微环境中免疫细胞的相对分布。我们的研究发现，MSC通过高度分泌CX3CL1招募CX3CR1高的巨噬细胞并促进M1极化，从而抑制肿瘤生长。与单药治疗相比，MSC和αPD1的联合治疗对CRC更有效。MSC通过促进M1巨噬细胞极化抑制CD8 + T细胞上的PD1表达，促进CD8 + T细胞增殖，从而提高CRC对αPD1治疗的敏感性。此外，在抑制MSC中CX3CL1的分泌后，以上治疗效果消失。我们基于MSC的免疫治疗策略同时招募和激活肿瘤部位的免疫效应细胞，表明MSC和αPD1的联合治疗可能是CRC的潜在治疗方案。版权所有©2023 Liu，Ma，Liu，Cheng，Li，Zhang，Zeng，Chen，Zhang和Hu。

Anti-PD1/PDL1 monotherapy has failed to acquire sufficiently ideal results in most solid tumors. Mesenchymal stem cells (MSCs) have been reported to exert therapeutic effects on some tumors, but the functions of MSCs in colorectal cancer (CRC) need further research. In this study, we aimed to investigate the therapeutic effect and the improvement of sensitivity of MSCs to anti-PD1 antibodies (αPD1) in CRC and to evaluate the possible mechanism. The relative distribution of immune cells in tumor microenvironment was examined after the mice were treated with MSC and/or αPD1. Our study revealed that MSC recruits CX3CR1high macrophages and promotes M1 polarization to inhibit tumor growth via highly secretion of CX3CL1.The combination of MSC and αPD1 was superior to monotherapy against CRC. MSC inhibits PD1 expression on CD8+ T cells by facilitating M1 macrophage polarization, which promotes the proliferation of CD8+ T cells, thus improving the sensitivity to αPD1 therapy in CRC. Additionally, the above therapeutic effect disappeared after inhibiting the secretion of CX3CL1 in MSC. Our MSC-based immunotherapeutic strategy simultaneously recruited and activated immune effector cells at the tumor site, suggesting that the combination of MSC and αPD1 could be a potential therapy for CRC.Copyright © 2023 Liu, Ma, Liu, Cheng, Li, Zhang, Zeng, Chen, Zhang and Hu.