2. Academic Validation
  3. 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

  • Cell Rep. 2023 Feb 9;42(2):112090. doi: 10.1016/j.celrep.2023.112090.
Tian Wei 1,  Kangxin Wang 2,  Shuting Liu 2,  Yunxuan Fang 2,  Zixi Hong 2,  Yingfu Liu 3,  Huimin Zhang 4,  Chaoyong Yang 1,  Gaoliang Ouyang 5,  Tiantian Wu 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China; Department of Hematology, the First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen 361003, China.
  • 2 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
  • 3 Department of Basic Medical Sciences, School of Medicine, Xiamen University, Xiamen 361102, China.
  • 4 Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province, Xiamen 361005, China.
  • 5 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China; Department of Hematology, the First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen 361003, China. Electronic address: oygldz@xmu.edu.cn.
  • 6 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China; Department of Hematology, the First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen 361003, China. Electronic address: wutiantian@xmu.edu.cn.
PMID: 36773295 DOI: 10.1016/j.celrep.2023.112090
Abstract

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.

Keywords

CP: Cancer; CP: Immunology; PD-1; colorectal cancer; combination therapy; periostin; tumor-associated macrophages.

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