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XCR1+ and CD11b+ migratory dendritic cells cooperate for the crosspriming of intratumoral CD8+ T cells with a tissue-resident memory phenotype [RNA-Seq]

ABSTRACT: The composition and diversity of tumor-infiltrating CD8+ T cell populations have important consequences on the development of anti-tumor immunity. In a murine model of lung cancer, we have addressed the role of dendritic cell subsets on the generation of various types of tumor-infiltrating CD8+ T cells. We show that CD44+PD1- effector and PD1+TIM3+ exhausted, tumor-infiltrating CD8+ T cells require XCR1+ DC1s but not IRF4-dependent CD11b+ DC2s. By contrast, CD103+CD69+ TRM-like, tumor-infiltrating CD8+ T cells require both DC1s and DC2s. The same requirement is found in tumor-draining lymph nodes where we identify CD103+ TRM-like precursors that are dependent on both XCR1+ DC1s and CD11b+, migratory DC2s. Mechanistically, we evidence that both types of migratory DCs cooperate. Mild TCR triggering by low MHCI-peptide density at the surface of cross-presenting migratory DC2s and low IL-12 support TGFb-dependent TRM specification in lymph nodes. High TCR triggering and high MHCI-peptide density at the surface of cross-presenting migratory DC1s and high IL-12 support proliferative expansion and CXCR6 acquisition. Altogether, these findings highlight the induction of intratumoral TRM-like cells under the collective aegis of multiple DCs subsets within tumor-draining lymph nodes reconciliating TRM phenotype instruction with proliferative expansion.

ORGANISM(S): Mus musculus

PROVIDER: GSE337601 | GEO | 2026/07/07

REPOSITORIES: GEO

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XCR1+ and CD11b+ migratory dendritic cells cooperate for the crosspriming of intratumoral CD8+ T cells with a tissue-resident memory phenotype

Project description:The composition and diversity of tumor-infiltrating CD8+ T cell populations have important consequences on the development of anti-tumor immunity. In a murine model of lung cancer, we have addressed the role of dendritic cell subsets on the generation of various types of tumor-infiltrating CD8+ T cells. We show that CD44+PD1- effector and PD1+TIM3+ exhausted, tumor-infiltrating CD8+ T cells require XCR1+ DC1s but not IRF4-dependent CD11b+ DC2s. By contrast, CD103+CD69+ TRM-like, tumor-infiltrating CD8+ T cells require both DC1s and DC2s. The same requirement is found in tumor-draining lymph nodes where we identify CD103+ TRM-like precursors that are dependent on both XCR1+ DC1s and CD11b+, migratory DC2s. Mechanistically, we evidence that both types of migratory DCs cooperate. Mild TCR triggering by low MHCI-peptide density at the surface of cross-presenting migratory DC2s and low IL-12 support TGFb-dependent TRM specification in lymph nodes. High TCR triggering and high MHCI-peptide density at the surface of cross-presenting migratory DC1s and high IL-12 support proliferative expansion and CXCR6 acquisition. Altogether, these findings highlight the induction of intratumoral TRM-like cells under the collective aegis of multiple DCs subsets within tumor-draining lymph nodes reconciliating TRM phenotype instruction with proliferative expansion.

2026-07-07 | GSE337798 | GEO

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Project description:The immune system undergoes a progressive functional remodeling with age, polarizing the immune responses toward a “killer” or “healer” phenotype. Understanding how the age bias shapes anti-tumor immunity is essential in designing effective immunotherapies. In this manuscript we explore the anti-tumor CD8+ T cell responses generated in young (prepubescent) and adult (pre-senescent) mice. Using an MHCI-deficient, trackable tumor model, we observed that tumor reactive CD8+ T cells that expanded in young tumor-bearing (TB) mice acquired a terminally differentiated phenotype characterized by overexpression of inhibitory receptors and the transcription factor Tox1. Furthermore, tumor infiltrating CD8+ T cells from young tumors yielded a poor cytokine response compared to CD8+ T cells infiltrating adult tumors. Young migratory dendritic cells (migDC) and mononuclear phagocytic cells (MPCs) infiltrating young tumors were more competent in capturing and cross-presenting tumor antigen, leading to enhanced priming of CD8+ T cells in the draining lymph nodes (dLNs), and their subsequent terminal differentiation in the tumors. Notably, single-cell transcriptional profiling of tumor infiltrating MPCs revealed that young MPCs are polarized toward an inflammatory, effector phenotype. Consistent with our observations in young vs adult TB mice, analysis of immune infiltrates from pediatric solid tumors revealed a significant correlation between tumor-infiltrating CD8+ T cells with an exhaustion phenotype and the frequency of PD-L1-expressing phagocytic cells. Collectively, these data indicate that the young microenvironment of an actively developing tissue contributes to the generation of an immune response skewed toward a terminal effector state, thus narrowing the window for immunotherapeutic interventions.

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Antigen cross-presentation in young tumor-bearing hosts promotes CD8 T cell terminal differentiation [gene expression]

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2024-02-14 | PXD031794 | Pride

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