CD4 T-cell immunotherapy for chronic viral infections and cancer

Immunotherapy. 2013 Sep;5(9):975-87. doi: 10.2217/imt.13.91.


During chronic infections and cancer, T cells progressively lose function and become exhausted. However, effective T-cell responses are necessary to ultimately control viral infections and tumors. Hence, strategies that either restore endogenous immune responses or provide functional T cells by adoptive immunotherapy need to be explored. CD8 T cells play a prominent role in viral infections, as well as cancer, but CD4 T cells are necessary to support CD8 T-cell function. In addition, CD4 T cells exert direct effector functions, induce optimal B-cell responses and orchestrate innate immunity. Therefore, we propose that adoptive transfer strategies should exploit CD4 T cells alone or in combination with CD8 T cells, for the treatment of chronic infections and cancer. Furthermore, since adoptively transferred cells are subject to exhaustion, combining adoptive transfer therapy with immunotherapies that inhibit T-cell exhaustion should maximize the longevity and success rate of responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adoptive Transfer / methods*
  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes* / immunology
  • CD4-Positive T-Lymphocytes* / transplantation
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Chronic Disease
  • Humans
  • Immunity, Innate
  • Neoplasms* / immunology
  • Neoplasms* / pathology
  • Neoplasms* / therapy
  • Virus Diseases* / immunology
  • Virus Diseases* / pathology
  • Virus Diseases* / therapy