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A distinct stimulatory cDC1 subpopulation amplifies CD8 T cell responses in tumors for protective anti-cancer immunity. | LitMetric

AI Article Synopsis

  • Type 1 conventional dendritic cells (cDC1) play a critical role in either promoting or hindering anti-cancer immunity by interacting with CD8 T cells in tumors.
  • Using advanced imaging and deep learning, researchers found that the clustering of cDC1 and CD8 T cells within tumor stroma is a key indicator of effective immune responses against cancer.
  • A specific subset of these cDC1 cells, characterized by CCR7, produces signaling molecules that facilitate T cell activation and growth, and their presence is linked to better survival outcomes in cancer patients, suggesting potential for therapeutic strategies.

Article Abstract

Type 1 conventional dendritic cells (cDC1) can support T cell responses within tumors but whether this determines protective versus ineffective anti-cancer immunity is poorly understood. Here, we use imaging-based deep learning to identify intratumoral cDC1-CD8 T cell clustering as a unique feature of protective anti-cancer immunity. These clusters form selectively in stromal tumor regions and constitute niches in which cDC1 activate TCF1 stem-like CD8 T cells. We identify a distinct population of immunostimulatory CCR7 cDC1 that produce CXCL9 to promote cluster formation and cross-present tumor antigens within these niches, which is required for intratumoral CD8 T cell differentiation and expansion and promotes cancer immune control. Similarly, in human cancers, CCR7 cDC1 interact with CD8 T cells in clusters and are associated with patient survival. Our findings reveal an intratumoral phase of the anti-cancer T cell response orchestrated by tumor-residing cDC1 that determines protective versus ineffective immunity and could be exploited for cancer therapy.

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Source
http://dx.doi.org/10.1016/j.ccell.2023.06.008DOI Listing

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