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.