Vascular endothelial growth factor inhibitors promote antitumor responses via tumor microenvironment immunosuppression in advanced colorectal cancer.

Purpose: This study aims to investigate changes in the tumor immune environment of patients who underwent therapy with a vascular endothelial growth factor (VEGF) inhibitor for advanced colorectal cancer.

Methods: Patients ( = 135) with T3 or T4 colorectal cancer were included in this retrospective study. They were classified as follows: patients who had not received preoperative treatment (UPFRONT group,  = 54), who had received FOLFOX as preoperative chemotherapy (FOLFOX group,  = 55), and who had undergone resection after combination FOLFOX and bevacizumab as unresectable colorectal cancer (B-MAB group,  = 26). The number of cytotoxic T lymphocytes (CTLs), FOXP3 lymphocytes (including regulatory T cells (Tregs)), CD163 monocytes (including M2-type tumor-associated macrophages (TAM-M2 type)), and programmed cell death 1 (PD-1) lymphocytes was evaluated immunohistochemically in the cancer cell area (CC) and stromal cell area (ST) of surgical specimens, and compared among the three groups.

Results: The CTL population did not differ among the three groups in both areas. In the B-MAB group, the numbers of PD-1 cells in the ST, FOXP3 lymphocytes in both areas, and CD163monocytes in the ST was lower than that in the other two groups, and a correlation with the histological therapeutic effect was observed.

Conclusions: In advanced colorectal cancer, VEGF inhibitors may decrease the number of PD-1 cells and inhibit the infiltration of FOXP3 lymphocytes and CD163monocytes into the tumor environment.