Blood CD33(+)HLA-DR(-) myeloid-derived suppressor cells are increased with age and a history of cancer

Abstract

As we age, the composition of our peripheral leukocytes changes dramatically. Many of these alterations contribute to the general immune dysfunction that burdens the elderly, which in turn, contributes to increased susceptibility to disease. MDSCs represent a heterogeneous population of immunosuppressive leukocytes that are elevated in the peripheral blood of cancer patients. Given the relation between cancer incidence and age, this study examined the frequency of peripheral blood CD33(+)HLA-DR(-) MDSCs across three cohorts: healthy adults (19-59 years old), community-dwelling seniors (61-76 years old), and frail elderly (67-99 years old). This analysis is the first to demonstrate that MDSCs and specifically the CD11b(+)CD15(+) MDSC subset are increased with age. Proinflammatory cytokines that are required for the differentiation of MDSCs (e.g., TNF-α, IL-6, and IL-1β) were similarly found to be increased in the serum of the frail elderly. Furthermore, the proportion of MDSCs and the CD11b(+)CD15(+) subset were found to be elevated significantly in elderly donors with a history of cancer. This age-related elevation in the frequency of MDSCs may contribute to the increased cancer incidence that occurs with age. Further investigation into the functional consequences of elevated MDSCs will provide valuable insight into the progression of age-related pathologies.

Figure 1.. MDSCs and CD11b⁺CD15⁺ MDSCs are increased with age.

The frequency of CD45⁺ leukocytes and proportions of monocytes, MDSCs, and the CD11b⁺CD15⁺ subsets were measured in adults, community-dwelling seniors, and frail elderly. Comparisons were performed by linear regression on log-transformed values, adjusting for sex, with P values adjusted to control for FDR. ***P < 0.001; **P < 0.01; *P < 0.05.

Figure 2.. Serum concentrations of proinflammatory cytokines are increased in the frail elderly (FE; n=30, average age=80) relative to adult donors (AD; n=10, average age=31).

For IFN-γ, 60% of adult donors did not meet the limit of detection; for IL-1β, all of the adults and 60% of frail elderly donors did not meet the limit of detection. Differences determined by the Kruskal-Wallis test with adjustments to control for FDR. ***P < 0.001; **P < 0.01; *P < 0.05.