Language
English
Publication Date
7-8-2024
Journal
Cancer Cell
DOI
10.1016/j.ccell.2024.05.025
PMID
38906155
PMCID
PMC11413804
PubMedCentral® Posted Date
7-8-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
Tumor-specific CD8+ T cells are frequently dysfunctional and unable to halt tumor growth. We investigated whether tumor-specific CD4+ T cells can be enlisted to overcome CD8+ T cell dysfunction within tumors. We find that the spatial positioning and interactions of CD8+ and CD4+ T cells, but not their numbers, dictate anti-tumor responses in the context of adoptive T cell therapy as well as immune checkpoint blockade (ICB): CD4+ T cells must engage with CD8+ T cells on the same dendritic cell during the effector phase, forming a three-cell-type cluster (triad) to license CD8+ T cell cytotoxicity and cancer cell elimination. When intratumoral triad formation is disrupted, tumors progress despite equal numbers of tumor-specific CD8+ and CD4+ T cells. In patients with pleural mesothelioma treated with ICB, triads are associated with clinical responses. Thus, CD4+ T cells and triads are required for CD8+ T cell cytotoxicity during the effector phase and tumor elimination.
Keywords
Humans, CD8-Positive T-Lymphocytes, Animals, CD4-Positive T-Lymphocytes, Mice, Immunotherapy, Neoplasms, Immune Checkpoint Inhibitors, Mice, Inbred C57BL, Immunotherapy, Adoptive, Dendritic Cells, Cell Line, Tumor, Tumor Microenvironment
Published Open-Access
yes
Recommended Citation
Espinosa-Carrasco, Gabriel; Chiu, Edison; Scrivo, Aurora; et al., "Intratumoral Immune Triads Are Required for Immunotherapy-Mediated Elimination of Solid Tumors" (2024). Faculty, Staff and Students Publications. 6315.
https://digitalcommons.library.tmc.edu/baylor_docs/6315