CD4(+) T cells with convergent TCR recombination reprogram stroma and halt tumor progression in adoptive therapy Journal Article
| Authors: | Wolf, S. P.; Leisegang, M.; Steiner, M.; Wallace, V.; Kiyotani, K.; Hu, Y.; Rosenberger, L.; Huang, J.; Schreiber, K.; Nakamura, Y.; Schietinger, A.; Schreiber, H. |
| Article Title: | 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. TCRs represented by single T cell clonotypes were similarly effective only if they shared CDR elements with preferentially selected TCRs in both α and β chains. Selecting candidate TCRs on the basis of these characteristics can help identify TCRs that are potentially therapeutically effective. |
| Keywords: | genetics; mouse; animal; animals; mice; mice, inbred c57bl; transgenic mouse; c57bl mouse; mice, transgenic; immunology; genetic recombination; receptors, antigen, t-cell; recombination, genetic; cd4+ t lymphocyte; cd4-positive t-lymphocytes; adoptive immunotherapy; immunotherapy, adoptive; lymphocyte antigen receptor; procedures; humans; human; female |
| Journal Title: | Science Immunology |
| Volume: | 9 |
| Issue: | 99 |
| ISSN: | 2470-9468 |
| Publisher: | Amer Assoc Advancement Science |
| Date Published: | 2024-09-01 |
| Start Page: | eadp6529 |
| Language: | English |
| DOI: | 10.1126/sciimmunol.adp6529 |
| PUBMED: | 39270007 |
| PROVIDER: | scopus |
| PMCID: | PMC11560124 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
