Intratumoral Treg ablation is sufficient to mediate tumor control systemically without autoimmunity
Year: 2025
Type: preprint
Abstract: ABSTRACT Regulatory T cells (T regs ) 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 Foxp3 DTR mice to deplete IT T regs while leaving peripheral T regs intact. IT delivery of DT reduced T reg 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 T reg ablation. Mechanistically, IT T regs 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 T reg -depleting anti-CCR8 antibody and reveal a distinct therapeutic strategy that leverages cDC2s and CD4 + T cells.
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: National Institutes of Health
OpenAlex ID: W4411915932