Natural aging, association with peptides matching human endogenous retrovirus genes, and treatment response

抄録

Introduction: We previously reported that the certain peptides decrease after age ≥65 years. To evaluate their clinical significance, we assessed the association between natural aging and peptides matching human endogenous retrovirus genes.

Patients and Methods: We recruited participants (n = 2,035) from an earlier report who were classified into the following peptide groups (PGs) according to age: Age80PG, Age49PG, Age65PG, Age65-79PG, and Age65-79_AP_VpuPG. Next, we examined the frequency of human leucocyte antigens (HLAs) in PGs of HLA groups (HGs) and evaluated the survival outcomes in both PGs and HGs. We assessed whether HLAs could predict the treatment response. Some patients were examined for peripheral T-cell subpopulations at baseline and one year after surgery.

Results: Most patients belonged to PGs which increased frequency among patients age ≥80 years. The Age80PGlowHGs with a high frequency of PGs, low frequency of HLAs, and age ≥80 years showed no significant increase of CD8+ cells at one year after surgery, which resulted in detrimental survival outcomes, while the Age65PGhighHG cohort, with a low frequency of PGs, high frequency of HLAs, and age ≥65 years, presented significantly increased CD8+ cells at one year after surgery, which resulted beneficial survival outcomes. We predicted that although the overall Age80PGlowHG cohort harboring HLA-A33, or -B44, or -B56, or -DR13, would show detrimental survival outcomes, family history (+) females would respond positively to fluoropyrimidine antimetabolites therapy.

Conclusion: Our findings offer new insights into the balance between beneficial and detrimental effects of natural aging on cancer therapy.