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

Abstract

Abstract 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.

Keywords

• CD8+ T‐lymphocytes
• colorectal neoplasms
• LOX‐1
• macrophage
• myeloid‐derived suppressor cells
• prognosis