Abstract
Adjuvant chemotherapy in breast cancer patients causes immune cell depletion at an age when the regenerative capacity is compromised. Successful regeneration requires the recovery of both quantity and quality of immune cell subsets. Although immune cell numbers rebound within a year after treatment, it is unclear whether overall compositional diversity is recovered. We investigated the regeneration of immune cell complexity by comparing peripheral blood mononuclear cells from breast cancer patients ranging from 1-5 years after chemotherapy with those of age-matched healthy controls using mass cytometry and T cell receptor sequencing. These data reveal universal changes in patients' CD4+ T cells that persisted for years and consisted of expansion of Th17-like CD4 memory populations with incomplete recovery of CD4+ naive T cells. Conversely, CD8+ T cells fully recovered within a year. Mechanisms of T cell regeneration, however, were unbiased, as CD4+ and CD8+ T cell receptor diversity remained high. Likewise, terminal differentiated effector memory cells were not expanded, indicating that regeneration was not driven by recognition of latent viruses. These data suggest that, while CD8+ T cell immunity is successfully regenerated, the CD4 compartment may be irreversibly affected. Moreover, the bias of CD4 memory toward inflammatory effector cells may impact responses to vaccination and infection.
Highlights
With improving cancer survival rates, the number of individuals with a history of chemotherapy treatment is steadily increasing
We investigated the regeneration of immune cell complexity by comparing peripheral blood mononuclear cells from breast cancer patients ranging from 1–5 years after chemotherapy with those of age-matched healthy controls using mass cytometry and T cell receptor sequencing
Longitudinal monitoring of differential white blood cell counts showed a decline of about 50% in peripheral total lymphocyte numbers upon chemotherapy treatment in our patient cohort — a decline that was recovered by 1 year after chemotherapy (Supplemental Figure 1)
Summary
With improving cancer survival rates, the number of individuals with a history of chemotherapy treatment is steadily increasing. There are currently more than 3 million women with a past or present history of breast cancer in the United States, many of whom have received adjuvant chemotherapy This treatment, highly effective, causes a massive depletion of cells in the immune system, including different types of lymphocytes such as NK cells, B cells, and T cells, at an age when the de novo generation of lymphocytes, T cells, is already significantly compromised [1]. Longitudinal studies have determined that immune cell populations have differential rates of recovery after chemotherapy treatment, with innate (e.g., NK cells, monocytes) populations generally recovering to pretreatment numbers more rapidly than adaptive (e.g., T cells, B cells) populations These studies demonstrate that the recovery of B cells occurs within 6–12 months, even surpassing pretreatment levels during this time [3]. Whether the overall quality of the adaptive immune system is fully recovered during this time period is unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
