Immune reconstitution following high-dose chemotherapy with stem cell rescue in patients with advanced breast cancer

The present study examines the nature of humoral and cellular immune recons titution in 28 patients with advanced breast cancer following high-dose che motherapy with stem cell rescue, patients underwent testing of T, B, NK and dendritic cell function at serial time points until 1 year post transplant or until the time of disease progression. Abnormalities in T cell phenotyp e and function were observed following high-dose chemotherapy that persiste d for at least 6-12 months. The vast majority of patients experienced an in version of the CD4/CD8 ratio and demonstrated an anergic response to candid a antigen. Mean T cell proliferation in response to PHA and to co-culture w ith allogeneic monocytes was significantly compromised. In contrast, mean I ge and IgA levels were normal 6 months post transplant and NK cell yields a nd function were transiently elevated following high-dose chemotherapy. Den dritic cells generated from peripheral blood progenitors displayed a charac teristic phenotype and were potent inducers of allogeneic T cell proliferat ion in the post-transplant period. The study demonstrates that patients und ergoing autologous transplantation for breast cancer experience a prolonged period of T cell dysfunction, In contrast, B, NK, and DC recover more rapi dly. These findings carry significant implications for the design of post-t ransplant immunotherapy.