Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

• Published in: Trends in immunology Vol. 26; no. 2; pp. 111 - 117
• Main Authors: Klebanoff, Christopher A., Khong, Hung T., Antony, Paul A., Palmer, Douglas C., Restifo, Nicholas P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2005
• Subjects: Animals; Antigen-Presenting Cells - drug effects; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - radiation effects; Clinical Trials as Topic; Humans; Immune Tolerance - immunology; Immunotherapy, Adoptive; Interleukin Receptor Common gamma Subunit; Interleukins - immunology; Interleukins - therapeutic use; Lymphocyte Activation - immunology; Lymphocyte Depletion; Models, Immunological; Neoplasms - immunology; Neoplasms - therapy; Receptors, Interleukin-7 - immunology; T-Lymphocytes - immunology; T-Lymphocytes - transplantation; Treatment Outcome
• ISSN: 1471-4906; 1471-4981
• DOI: 10.1016/j.it.2004.12.003

Lymphodepletion followed by adoptive cell transfer (ACT) of autologous, tumor-reactive T cells boosts antitumor immunotherapeutic activity in mouse and in humans. In the most recent clinical trials, lymphodepletion together with ACT has an objective response rate of 50% in patients with solid metastatic tumors. The mechanisms underlying this recent advance in cancer immunotherapy are beginning to be elucidated and include: the elimination of cellular cytokine ‘sinks’ for homeostatic γ C-cytokines, such as interleukin-7 (IL-7), IL-15 and possibly IL-21, which activate and expand tumor-reactive T cells; the impairment of CD4 +CD25 + regulatory T (Treg) cells that suppress tumor-reactive T cells; and the induction of tumor apoptosis and necrosis in conjunction with antigen-presenting cell activation. Knowledge of these factors could be exploited therapeutically to improve the in vivo function of adoptively transferred, tumor-reactive T cells for the treatment of cancer.