CD4⁺ T cells with convergent TCR recombination reprogram stroma and halt tumor progression in adoptive therapy

Cancers eventually kill hosts even when infiltrated by cancer-specific T cells. We examined whether cancer-specific T cell receptors of CD4^(+) T cells (CD4TCRs) from tumor-bearing hosts can be exploited for adoptive TCR therapy. We focused on CD4TCRs targeting an autochthonous mutant neoantigen that is only presented by stroma surrounding the MHC class II-negative cancer cells. The 11 most common tetramer-sorted CD4TCRs were tested using TCR-engineered CD4^(+) T cells. Three TCRs …