Intratumoral Treg ablation is sufficient to mediate tumor control systemically without autoimmunity
Bockman, A.; Gittins, B.; Zhang, C.; Hung, J.; Moreno Ayala, M.; Saddier Axe, D.; Weist, B. M.; DuPage, M.
Show abstract
Regulatory T cells (Tregs) infiltrate most tumors, yet whether they suppress immune responses directly within tumor tissues is not clear. We used intratumoral (IT) delivery of diphtheria toxin (DT) in Foxp3DTR mice to deplete IT Tregs while leaving peripheral Tregs intact. IT delivery of DT reduced Treg frequencies in the tumor, which promoted potent tumor control without autoimmunity. Interestingly, this control was principally mediated by CD4+ T cells, whereas CD8+ T cells only contributed when CD4+ T cells were absent. While conventional dendritic cells (cDCs) were required to clear tumors, Batf3+ cDC1s were dispensable. Distant secondary tumors, mimicking metastases, were also controlled by IT Treg ablation. Mechanistically, IT Tregs suppressed antitumor T cell responses by blocking the acquisition of tumor antigen by cDC2s. Importantly, similar mechanisms of control were observed using a clinically translatable IT Treg-depleting anti-CCR8 antibody and reveal a distinct therapeutic strategy that leverages cDC2s and CD4+ T cells.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Desmoplastic stroma restricts T cell extravasation and mediates immune exclusion and immunosuppression in solid tumors 97%
- Regulatory T cells crosstalk with tumor and endothelium through lymphotoxin signaling 97%
- Rapid establishment of a tumor-retained state curtails the contribution of conventional NK cells to anti-tumor immunity in solid cancers 97%
Similar papers in this journal
- Intratumor Childhood Vaccine-Specific CD4+ T cell Recall Coordinates Antitumor CD8+ T cells and Eosinophils 98%
- Distinct sets of molecular characteristics define tumor-rejecting neoantigens 97%
- Deep immune profiling reveals targetable mechanisms of immune evasion in checkpoint blockade-refractory glioblastoma 97%
Similar papers in this journal
- Lung cancer-intrinsic SOX2 expression mediates resistance to checkpoint blockade therapy by inducing Treg-dependent CD8+ T cell exclusion 97%
- Microenvironmental correlates of immune checkpoint inhibitor response in human melanoma brain metastases revealed by T cell receptor and single-cell RNA sequencing 96%
- Targeting macrophages with CAR-T cells delays solid tumor progression and enhances anti-tumor immunity 96%
Similar papers in this journal
- Cancer-cell-derived cGAMP limits the activity of tumor-associated CD8+ T cells 98%
- Neoantigen Cancer Vaccines and Different Immune Checkpoint Therapies Each Utilize Both Converging and Distinct Mechanisms that in Combination Enable Synergistic Therapeutic Efficacy 97%
- Inflammatory cytokines mediate the induction of and awakening from metastatic dormancy 97%
Similar papers in this journal
- Cell lineage as a predictor of immune response in neuroblastoma 95%
- Cancer-associated fibroblast compositions change with breast cancer progression linking S100A4 and PDPN ratios with clinical outcome 95%
- Glutamine mimicry suppresses tumor progression through asparagine metabolism in pancreatic ductal adenocarcinoma 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.