Correlation between immune signature and high‐density lipoprotein cholesterol level in stage II/III colorectal cancer

An increasing amount of evidence suggests that high‐density lipoprotein cholesterol (HDL‐C) is related to a positive prognosis in various cancers. However, the correlation between HDL‐C and the immune signature and the prognostic role of HDL‐C in stage II/III colorectal cancer (CRC) has not been previously reported. A total of 667 CRC patients were enrolled and divided into two groups based on the lower limit of normal HDL‐C values (0.78 mmol/L). We used Kaplan‐Meier curves and the Cox regression model to analyze the prognostic role of HDL in both disease‐free survival (DFS) and overall survival (OS). Fifty‐five pairs of tumor tissues were selected according to the variation in HDL‐C levels (high or low) and the matched characterizes (ages, T stage, and N stage). Using immunohistochemistry, tumor tissues were stained with antibodies against CD3, CD8, CD163, iNOS, Forkhead box P3 (FOXP3), and CD33. We calculated the density of positively‐stained infiltrating cells in the tumor center (TC) and invasive margin (IM). We then used Spearman rank correlation to further investigate the relationship between HDL‐C levels and the immune signatures. Our results revealed that compared to patients with high HDL‐C levels, patients with low HDL‐C levels had poor 3‐year DFS (68.9% vs 83.1%, P = 0.032) and 5‐year OS rates (66.6% vs 85.3%, P = 0.002). We also identified a positive correlation between HDL‐C and CD3(+), CD8(+) and iNOS(+) cells and a negative correlation between HDL‐C and CD163(+) cells in both the TC and IM. This study reveals that a low HDL‐C level in stage II/III CRC patients predicts poor prognosis. The correlation between the HDL‐C level and immune signature in tissue specimens suggested that HDL‐C is likely to play an inhibitory role in tumor development via affecting immune responses.