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

Abstract

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.

Predictive value of a reduction in the level of high-density lipoprotein-cholesterol in patients with non-small-cell lung cancer undergoing radical resection and adjuvant chemotherapy: a retrospective observational study

“…The NSCLC patients in this study received surgical resection, and so the immune system may play an important part in the elimination of potential residual micro-metastases. The anti-tumor effect of HDL-C both in humans and in vivo are associated with altered immune responses [ 42 , 43 ]. Speculatively, chemotherapy-related HDL-C and survival may be explained by the interaction between the cancer type, chemotherapy regimen and the immune system.…”

Revealing the Role of High-Density Lipoprotein in Colorectal Cancer

“…Low pre-operative HDL-C levels in patients with stage II/III CRC are associated with worse disease-free survival (DFS) and overall survival (OS) [ 29 ]. On the other hand, chemotherapy-related elevations in HDL-C levels in patients with non-metastatic CRC correlate with a longer DSF and OS [ 25 ].…”

“…A bulk of evidence indicates that the antitumor activity of apoAI in various malignancies is partially related to its effects on immunity [ 66 ]. Indeed, it was recently shown that serum HDL-C levels correlate with the specific immune signature of cancerous tissue in CRC patients, in particular with CD3 and CD8 markers, implying that high HDL-C and apoAI levels might be associated with enhanced recruitment and activity of CD3+ and CD8+ T cells, which exhibit antitumor activities [ 29 ]. In addition, in vitro studies have demonstrated that apoAI mimetics inhibit the proliferation, migration, and invasiveness of human colon adenocarcinoma cell lines [ 67 ], as well as diminish the viability and proliferation of murine colon adenocarcinoma cells [ 67 ].…”

Lipid Metabolism Reprograming as a Target for Cancer

“…Cholesterol associate with LDL and HDL, or cholesterol derivatives are likely to have distinct and/or opposing effects [51][52][53][54][55]77]. Overall inhibition of fatty acid and/or cholesterol synthesis may thus induced complex outcomes.…”

“…One speculation is that altered lipid profiles elicit immune response and such induced immune suppression. Reprogramming of cellular cholesterol metabolism has been shown to modulate the immune system [77,97,98]. Lipotoxicity induced cell death may be another reason.…”