IL‐7 is superior to IL‐2 for <i>ex vivo</i> expansion of tumour‐specific CD4⁺ T cells

<jats:title>Abstract</jats:title><jats:p>It is well established that tumours hinder both natural and vaccine‐induced tumour‐specific CD4<jats:sup>+</jats:sup> T‐cell responses. Adoptive T‐cell therapy has the potential to circumvent functional tolerance and enhance anti‐tumour protective responses. While protocols suitable for the expansion of cytotoxic CD8<jats:sup>+</jats:sup> T cells are currently available, data on tumour‐specific CD4<jats:sup>+</jats:sup> T cells remain scarce. We report here that CD4<jats:italic><jats:sup>+</jats:sup></jats:italic> T cells sensitized to tumour‐associated Ag <jats:italic>in vivo</jats:italic>, proliferate <jats:italic>in vitro</jats:italic> in response to IL‐7 without the need for exogenous Ag stimulation and accumulate several folds while preserving a memory‐like phenotype. Both cell proliferation and survival accounts for the outgrowth of tumour‐sensitized T cells among other memory and naive lymphocytes following exposure to IL‐7. Also IL‐2, previously used to expand anti‐tumour CTL, promotes tumour‐specific CD4<jats:sup>+</jats:sup> T‐cell accumulation. However, IL‐7 is superior to IL‐2 at preserving lymphocyte viability, <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic>, maintaining those properties, that are required by helper CD4<jats:sup>+</jats:sup> T cells to confer therapeutic efficacy upon transplantation in tumour‐bearing hosts. Together our data support a unique role for IL‐7 in retrieving memory‐like CD4<jats:sup>+</jats:sup> T cells suitable for adoptive T‐cell therapy.</jats:p>