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

ABSTRACT: 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 were characterized by convergent recombination for which multiple T cell clonotypes differed in their nucleotide sequences but encoded identical TCR α and β chains. These preferentially selected TCRs destroyed tumors equally well and halted progression through reprogramming of the tumor stroma. TC

SUBMITTER: Wolf SP 

PROVIDER: S-EPMC11560124 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature