Thymulin linked age-related inflammation to antitumor immunity in models of aged mice

A thymic peptide made tumors in aged mice responsive to immunotherapy

On July 21, a Nature Communications paper reported that thymulin, a thymic peptide, reduced age-related inflammation in aged mice and improved the efficacy of PD-L1 blockade against their tumors. This peptide has not yet been administered to humans.

The thymus is the organ where T-cells mature. The researchers tested whether a peptide secreted by the thymus could reduce inflammation in monocytes and macrophages, cells that protect the body from infection. With age, these cells become more likely to release the inflammatory proteins IL-1α, IL-1β, IL-6 and TNF-α. The authors link this change to a weaker T-cell response against tumors.

To distinguish changes intrinsic to bone marrow cells from signals produced by other tissues, the researchers joined the circulatory systems of young and aged mice, then transplanted bone marrow between them. Among the circulating signals, they identified thymulin, a thymic peptide whose activity declines with age.

In the July 21 paper, one week of thymulin injections reduced the proportion of myeloid cells producing inflammatory proteins in aged mice. In cell experiments, the peptide inhibited NF-κB, a protein that activates inflammatory genes.

The authors also found that healthy donors from 21 to 87 years of age had progressively more inflammatory myeloid cells with age. When blood cells were treated with thymulin in vitro, they released lower amounts of the same proteins. The researchers tested the antitumor effect only in aged mice.

In breast cancer models, thymulin slowed tumor growth, increased the number of T-cells producing IFN-γ, and extended the survival of the mice. An antibody against PD-L1 removes one of the inhibitory signals that restrain the T-cell response and allow tumors to evade immune attack. Combining thymulin with this antibody made tumors in aged mice responsive to PD-L1 blockade.