Immune reconstitution following high-dose chemotherapy with stem cell rescue in patients with advanced breast cancer
David Avigan,Zekui Wu,Robin Joyce,Anthony D. Elias,Paul G. Richardson,David F. McDermott,James D. Levine,L Kennedy,Nancy Giallombardo,D Hurley,Jianlin Gong,Donald Kufe +11 more
TLDR
It is demonstrated that patients undergoing autologous transplantation for breast cancer experience a prolonged period of T cell dysfunction, in contrast to B, NK, and DC recover more rapidly, which carries significant implications for the design of post-transplant immunotherapy.Abstract:
The present study examines the nature of humoral and cellular immune reconstitution in 28 patients with advanced breast cancer following high-dose chemotherapy 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 phenotype and function were observed following high-dose chemotherapy that persisted for at least 6-12 months. The vast majority of patients experienced an inversion of the CD4/CD8 ratio and demonstrated an anergic response to candida antigen. Mean T cell proliferation in response to PHA and to co-culture with allogeneic monocytes was significantly compromised. In contrast, mean IgG and IgA levels were normal 6 months post transplant and NK cell yields and function were transiently elevated following high-dose chemotherapy. Dendritic cells generated from peripheral blood progenitors displayed a characteristic phenotype and were potent inducers of allogeneic T cell proliferation in the post-transplant period. The study demonstrates that patients undergoing autologous transplantation for breast cancer experience a prolonged period of T cell dysfunction. In contrast, B, NK, and DC recover more rapidly. These findings carry significant implications for the design of post-transplant immunotherapy.read more
Citations
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Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses.
David Avigan,Baldev Vasir,Jianlin Gong,Virginia F. Borges,Zekui Wu,Lynne Uhl,Michael B. Atkins,James W. Mier,David F. McDermott,Therese Smith,Nancy Giallambardo,Carolyn Stone,Kim Schadt,Jennifer Dolgoff,Jean Claude Tetreault,Marisa Villarroel,Donald Kufe +16 more
TL;DR: The findings demonstrate that fusion cell vaccination of patients with metastatic breast and renal cancer is a feasible, nontoxic approach associated with the induction of immunological and clinical antitumor responses.
Journal ArticleDOI
Immune restoration following hematopoietic stem cell transplantation : an evolving target
TL;DR: The current understanding for IR following HSCT is reviewed and the novel ways in which to restore immune function and decrease transplant-related toxicity in the transplant recipient are reviewed.
Journal ArticleDOI
Prolonged survival associated with early lymphocyte recovery after autologous hematopoietic stem cell transplantation for patients with metastatic breast cancer.
TL;DR: Evaluating patients with metastatic breast cancer who underwent ASCT at the Mayo Clinic from 1994 to 1999 found that ALC ⩾500 cells/μl on day 15 post-ASCT was associated with significantly better survival, suggesting the importance of early immune recovery post-asCT in these patients.
Journal ArticleDOI
Significant Impairment in Immune Recovery After Cancer Treatment
TL;DR: Overall, immune recovery was poorer for interferon-&ggr;, IL-2,IL-4, lymphocyte proliferation, and natural killer cell activity than was for CD subsets and IL-6, and the type of cancer adjuvant therapy showed selective influence on immune recovery.
Journal Article
Influence of adjuvant hormone therapy and chemotherapy on the immune system analysed in the bone marrow of patients with breast cancer.
E. F. Solomayer,Markus Feuerer,Lianhua Bai,Victor Umansky,Philipp Beckhove,Gabriele C. Meyberg,Gunther Bastert,Volker Schirrmacher,Ingo Diel +8 more
TL;DR: Findings suggest profound and long-lasting negative effects on the bone marrow immune system by present day adjuvant therapy in breast cancer.
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