Facilitates M2 Macrophage Polarization and Colorectal Carcinoma Progression by Activating TLR4/NF-B/S100A9 Cascade.

() has been considered as a significant contributor in promoting colorectal carcinoma (CRC) development by suppressing host anti-tumor immunity. Recent studies demonstrated that the aggregation of M2 macrophage (M) was involved in CRC progress driven by infection. However, the underlying molecular mechanisms are poorly characterized. Here, we investigated the role of in M polarization as well as its effect on CRC malignancy. infection facilitated differentiation of M into the M2-like M phenotype by study. Histological observation from -positive CRC tissues confirmed the abundance of tumor-infiltrating M2-like M. -induced M2-like M polarization was weakened once inhibiting a highly expressed damage-associated molecular pattern (DAMP) molecule S100A9 mainly derived from -challenged M and CRC cells. In addition, -challenged M2-like M conferred CRC cells a more malignant phenotype, showing stronger proliferation and migration characteristics and significantly enhanced tumor growth , all of which were partially inhibited when S100A9 was lost. Mechanistic studies further demonstrated that activation of TLR4/NF-B signaling pathway mediated -induced S100A9 expression and subsequent M2-like M activation. Collectively, these findings indicate that elevated S100A9 in -infected CRC microenvironment participates in M2-like M polarization, thereby facilitating CRC malignancy. Furthermore, targeting TLR4/NF-B/S100A9 cascade may serve as promising immunotherapeutic strategy for -associated CRC.