Systemic CD4 Immunity and PD-L1/PD-1 Blockade Immunotherapy

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Abstract
PD-L1/PD-1 blockade immunotherapy has changed the therapeutic approaches for the treatment of many cancers. Nevertheless, the mechanisms underlying its efficacy or treatment failure are still unclear. Proficient systemic immunity seems to be a prerequisite for efficacy, as recently shown in patients and in mouse models. It is widely accepted that expansion of anti-tumor CD8 T cell populations is principally responsible for anti-tumor responses. In contrast, the role of CD4 T cells has been less studied. Here we review and discuss the evidence supporting the contribution of CD4 T cells to anti-tumor immunity, especially recent advances linking CD4 T cell subsets to efficacious PD-L1/PD-1 blockade immunotherapy. We also discuss the role of CD4 T cell memory subsets present in peripheral blood before the start of immunotherapies, and their utility as predictors of response.
Funding Information
  • Spanish Association Against Cancer (PROYE16001ESCO)
  • Instituto de Salud Carlos III (ISCIII)-FEDER (FIS PI17/02119, FIS PI20/00010, COV20/00000, TRANSPOCART ICI19/00069)
  • Department of Health of the Government of Navarre (BMED 050-2019)
  • Department of Industry, Government of Navarre (0011-1411-2020-000013, 0011-1411-2020-000033, 0011-1411-2019-000058)
  • European Union’s Horizon 2020 Research and Innovation Programme (848166)

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