Periostin deficiency reduces PD-1+ tumor-associated macrophage infiltration and enhances anti-PD-1 efficacy in colorectal cancer

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. [Display omitted] •Periostin deficiency reduces PD-1+ TAM infiltration in the CRC tissues•Periostin promotes the expression of PD-1 on TAMs by integrin-NF-κB signaling•Periostin deficiency downregulates PD-L1 on tumor cells via IL-6 and IFN-γ•Combined inhibition of periostin and PD-1 significantly suppresses CRC progression Wei et al. show that periostin recruits programmed death receptor 1 (PD-1+) tumor-associated macrophages (TAMs) through integrin-nuclear factor κB (NF-κB) signaling in colorectal cancer (CRC). Periostin deficiency decreases the infiltration of PD-1+ TAMs, which promote immune escape by inducing the expression of PD-L1 on colorectal tumor cells. Blocking periostin and PD-1 inhibits CRC progression.