Periostin deficiency reduces PD-1+ tumor-associated macrophage infiltration and enhances anti-PD-1 efficacy in colorectal cancer.
Periostin deficiency reduces PD-1+ tumor-associated macrophage infiltration and enhances anti-PD-1 efficacy in colorectal cancer.
复制标题
DOI：
10.1016/j.celrep.2023.112090
复制
发表时间：
2023-02
期刊：
影响因子：
8.8
通讯作者：
Tian Wei;Kangxin Wang;Shuting Liu;Yunxuan Fang;Zi-Xuan Hong;Yingfu Liu;Huimin Zhang;Chaoyong Yang;G. Ouyang;Tiantian Wu
中科院分区：
文献类型：
--
作者：
Tian Wei;Kangxin Wang;Shuting Liu;Yunxuan Fang;Zi-Xuan Hong;Yingfu Liu;Huimin Zhang;Chaoyong Yang;G. Ouyang;Tiantian Wu
Periostin是一种多功能的胞外蛋白，在炎症性疾病和肿瘤的发生中发挥着重要作用。我们以前的工作已经证明，Periostin缺乏抑制结直肠癌(CRC)的进展。在此，我们旨在阐明Periostin在结直肠癌免疫微环境中的作用。我们发现，Periostin缺乏显著减少了程序性死亡受体1(PD-1)+肿瘤相关巨噬细胞(TAMS)在结直肠癌组织中的渗透。Periostin通过整合素-核因子κB(NF-κB)信号通路促进TAMs表面PD-1的表达，PD-1+TAMs产生白介素6(IL-6)和干扰素γ(干扰素γ)诱导结直肠癌细胞表达PD-L1。此外，与单独抑制Periostin或PD-1相比，联合抑制Periostin和PD-1可显著抑制CRC进展。综上所述，我们的结果提示，在结直肠癌中，Periostin缺乏减少了PD-1+TAMs的渗透，并增强了抗PD-1治疗的疗效。
Periostin, a multifunctional extracellular protein, plays an important role in inflammatory disorders and tumorigenesis. Our previous work has demonstrated that periostin deficiency inhibits colorectal cancer (CRC) progression. Here, we aim to clarify the role of periostin in the immune microenvironment of CRC. We find that periostin deficiency significantly decreases the infiltration of programmed death receptor 1 (PD-1)+tumor-associated macrophages (TAMs) in CRC tissues. Periostin promotes the expression of PD-1 on TAMs by integrin-ILK-nuclear factor κB (NF-κB) signaling, and PD-1+TAMs produce interleukin-6 (IL-6) and interferon γ (IFN-γ) to induce the expression of PD-L1 on colorectal tumor cells. Moreover, combined inhibition of periostin and PD-1 significantly suppresses CRC progression compared with the inhibition of periostin or PD-1 alone. In summary, our results suggest that periostin deficiency reduces the infiltration of PD-1+TAMs and enhances the efficacy of anti-PD-1 treatment in CRC.