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

Trends Immunol. 2005 Feb;26(2):111-7. doi: 10.1016/


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 γC-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.

Publication types

  • Review

MeSH terms

  • 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


  • IL2RG protein, human
  • Interleukin Receptor Common gamma Subunit
  • Interleukins
  • Receptors, Interleukin-7