Low level of stromal lectin-like oxidized LDL receptor 1 and CD8 cytotoxic T-lymphocytes indicate poor prognosis of colorectal cancer.

Background: Lectin-like oxidized LDL receptor-1 (LOX-1) has been identified as a new marker for functional myeloid-derived suppressor cells (MDSCs) that exhibit an immunosuppressive phenotype in the tumor microenvironment (TME). However, the role of LOX-1 cells in the TME of colorectal cancer (CRC) remains unknown.

Aim: This study aimed to determine the expression and significance of LOX-1 in the TME of clinical CRC specimens.

Methods And Results: We performed immunohistochemical and genetic analyses of LOX-1, CD8, KRAS, and BRAF in 128 resected CRC specimens and determined the expression of IFN-γ and IL-10 using real-time reverse transcription-polymerase chain reaction. We analyzed the correlation between LOX-1, TME factors, gene alteration, clinicopathological factors, and disease prognosis. The co-expression pattern of LOX-1, hematopoietic markers, and a fibroblast marker was evaluated using multiplex immunofluorescence staining. Low stromal LOX-1 expression and low intratumoral CD8 cytotoxic T-lymphocyte (CTL) status correlated with poor prognosis. Moreover, stromal LOX-1-low/CD8 CTL-low status was the most important independent prognostic factor of poor overall survival. Most of the LOX-1 stromal cells were positive for CD163 , indicating they were CD163 M2 macrophages.

Conclusions: The MDSC marker, LOX-1, was mainly expressed by M2 macrophages in CRC tissues. LOX-1 macrophages and CD8 CTLs may serve as useful biomarkers for predicting the prognosis of CRC.