Sex and Age-Based Differences in Immune Responses to a Peptide Vaccine for Melanoma in Two Clinical Trials

Little is known about the impact of patient age and biological sex on immune responses to melanoma vaccines, especially CD4⁺ T cell immune responses to peptides presented by Class II MHC molecules.

We assessed the impact of age and sex on CD4+ T cell and antibody responses to a mixture of six melanoma helper peptides (6MHP) and on CD8+ T cell responses when vaccinating with 12 class I MHC-restricted melanoma peptides (12MP) plus either 6MHP or a tetanus helper T cell peptide (Tet). We hypothesized that immune responses would be greater in men and in younger patients.

We found differences in immune response by sex, but they favored female patients and were only evident for helper T cell responses to Tet with a weak trend to higher T cell responses to 12MP in female patients vaccinated with 12MP + Tet. The age-based differences favored younger patients but only for immune response to 12MP when inoculated with 12MP + Tet.

These findings reinforce the importance of assessing sex- and age-based differences in immune responses to cancer vaccines and other immune therapies. There is also a need to understand the reasons for such differences.