The presence of tumor-infiltrating lymphocytes (TILs) lends credence to the theory that prostate cancer (PCa) growth results from the interaction of epithelial cancer cells with the host’s immune system. CD5 and CD6, 2 signal-transducing coreceptors essential in fine-tuning T cell responses, were accessory molecules that control TIL fate and interaction with the tumor microenvironment. While there was debate regarding the nature of the CD5 ligand, CD6 binds to CD166/ALCAM, a cell adhesion molecule important in the development and spread of epithelial malignancies, including PCa. For a study, researchers sought to determine the function of CD5, CD6, and CD166/ALCAM gene variations in PCa.

In germline DNA samples from 376 PCa patients, functionally significant CD5 (rs2241002 and rs2229177), CD6 (rs17824933, rs11230563, and rs12360861), and CD166/ALCAM (rs6437585, rs579565, rs1044243, and rs35271455) single nucleotide polymorphisms (SNPs) were genotyped. Generalized linear models and survival analyses were used to examine their relationship with PCa prognostic markers such as biochemical recurrence (BCR) and the International Society of Urological Pathology (ISUP) grade.

The minor CD6 rs12360861 AA and CD166/ALCAM rs579565AA genotypes were shown to be linked with earlier BCR, with hazard ratios of 2.65 (95% CI: 1.39-5.05, P=0.003) and 1.86 (95% CI: 1.02-3.39, P=0.043), respectively, according to proportional hazards regression. However, haplotype studies showed a relationship between the CD5 rs2241002C-rs2229177T haplotype and ISUP grade more or around 2, with an odds ratio of 1.52 (95% CI: 1.05-2.21, P=0.026). Individually, none of the investigated SNPs was substantially linked with ISUP grade.

The findings demonstrated the influence of gene variations implicated in modulating immune-epithelial cell adhesion (CD166/ALCAM) and lymphocyte activation (CD5, CD6) on PCa aggressiveness and recurrence, confirming a role for host immunological response in PCa pathogenesis.

 

Reference: onlinelibrary.wiley.com/doi/10.1002/pros.24407