ANGPT2 promotes angiogenesis and immunosuppressive microenvironment in colorectal cancer

The Angiopoietin-Tie2 system is crucial in tumor angiogenesis for colorectal cancer (CRC), while investigations into integrating angiopoietin-Tie2 into the booming immunotherapy are underway. Here, we investigated the expression patterns and prognostic value of the Angiopoietin-Tie2 system in CRC.

The expression patterns of angiopoietin-2 (ANGPT2) and angiopoietin-1 (ANGPT1), two major ligands of the angiopoietin-Tie2 system, as well as their correlation with clinical characteristics and prognosis were analyzed in The Cancer Genome Atlas (TCGA), and the related functions based on protein-protein interaction (PPI) networks in CRC were explored. The impact of ANGPT2 on tumor angiogenesis and immunity was validated in vitro and in vivo.

ANGPT2 expression is upregulated in CRC, while ANGPT1 shows an opposite trend, but neither affects clinical characteristics. Kaplan-Meier survival curves and multivariate Cox analysis suggest that only high expression of ANGPT2 is associated with a poor prognosis in CRC. ANGPT2 and ANGPT1 are mainly involved in regulation of vasculature and cell chemotaxis migration. Knockdown of ANGPT2 reduced angiogenesis in vitro, and suppressed the immunosuppressive microenvironment involving CXCL12, including recruitment and differentiation of monocytes, M2 polarization of macrophages and exclusion of effector T cells, ultimately suppressed tumor growth in vivo.

ANGPT2, rather than ANGPT1, likely plays a significant role in vascular regulation and immune landscape in CRC.