Flt3L enhances clonal diversification and selective expansion of intratumoral CD8+ T cells while differentiating into effector-like cells
Summary: PD-1 blockade enhances anti-tumoral CD8+ T cell responses via type 1 conventional dendritic cells (cDC1s), but how cDC1s change the properties of intratumoral CD8+ T cells remains to be determined. Here, we identified two populations of intratumoral CD8+ T cells distinguished by their expre...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-12-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724013743 |
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| Summary: | Summary: PD-1 blockade enhances anti-tumoral CD8+ T cell responses via type 1 conventional dendritic cells (cDC1s), but how cDC1s change the properties of intratumoral CD8+ T cells remains to be determined. Here, we identified two populations of intratumoral CD8+ T cells distinguished by their expression of asialo-ganglio-N-tetraosylceramide (asGM1). asGM1neg and asGM1posCD8+ T cells show enriched expression of genes characteristic for precursor exhausted T (Tpex) cells and terminally exhausted T (Tex) cells, respectively. The in situ expression of Flt3L or inhibition of PD-1 each promote the differentiation of asGM1negCD8+ T cells into asGM1posCD8+ T cells via interleukin-12 (IL-12) while also increasing the expression of Tpex and effector-like T cell-associated genes and their effector functions. Both interventions selectively expand CD8+ T cells, but only Flt3L expression broadens their T cell receptor (TCR) repertoire. These data indicate the distinct role of Flt3L in diversifying the TCR repertoire, offering potential solutions for immune checkpoint blockade-resistant cancers. |
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| ISSN: | 2211-1247 |