Abstract
Background
Colorectal cancer (CRC) is currently the third most prevalent cancer globally, with increasing cases and fatalities. The emergence of immunotherapies, particularly cancer vaccines, in preventing and treating CRC has led researchers to investigate the connection between the immune system and CRC. Diverse immunophenotypes have been identified to either promote or hinder the onset and progression of cancer and elucidating their precise impact on CRC can aid in creating immune-based preparations.
Methods
Using publicly available genetic data, this study employs an extensive two-sample Mendelian randomization (MR) analysis to investigate whether there is a causal relationship between 731 immune cell phenotypic traits and CRC. The study incorporates four types of immune signatures - median fluorescence intensity (MFI), relative cells (RC), absolute cells (AC), and morphological parameters (MP). To ensure accuracy, multiple sensitivity analyses were conducted to test for heterogeneity, horizontal pleiotropy, and robustness.
Results
29 exposure factors with a nominal causal relationship with colorectal cancer were screened. After correction by Bonferroni, two immune cell phenotypes still had a significant effect on CRC (P < 6.84E-5), including CD25 on activated CD4 regulatory T cell (IVW, P = 1.96E-05, OR = 0.714, 95%CI = 0.611 ~ 0.833) and CD3 on Terminally Differentiated CD8 + T cell (IVW, P = 2.76E-05, OR = 1.213, 95%CI = 1.108 ~ 1.328). None of the sensitivity analyses suggested significant heterogeneity or horizontal pleiotropism, demonstrating that our results were robust.
Conclusions
Our study analyzes the causal effects of immunophenotyping on CRC, contributing to the development of CRC immunoprevention and treatment.