TLR2 signaling uniquely destabilizes tumor Tregs to promote cancer immunotherapy
Campbell, T. F.; Castillo, J. G.; Fernandez, S.; Ventura, D. G.; Vickery, J.; Homentcovschi, S.; Hernandez, N. F.; Ybarra, J.; Portnoy, D. A.; DuPage, M.
Show abstract
A fundamental principle of immune responses is that innate immunity promotes adaptive immunity, but in the context of cancer immunity, the importance of innate receptor signaling is poorly defined. To study how Toll-like receptor (TLR) signaling contributes to cancer immunity, we used an attenuated strain of Listeria monocytogenes (Lm) that inhibits tumor growth in mice. We found that Lm stimulation of TLR2, but not TLR5 or TLR9, was essential for tumor control. As expected, TLR2 supported the priming of Lm-specific T cells in lymphoid tissues. However, TLR2 signaling in innate immune cells within tumors also destabilized Foxp3 expression in regulatory T cells (Tregs), a function that was not mediated by other TLRs. Reduced Treg function promoted tumor antigen cross-presentation by DC1s to enhance the functionality of recalled tumor-specific CD8+ T cells directly within tumors. These findings reveal a unique capacity for TLR2 signaling to diminish immunosuppression and promote cancer immunity.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Intratumor Childhood Vaccine-Specific CD4+ T cell Recall Coordinates Antitumor CD8+ T cells and Eosinophils 97%
- Distinct sets of molecular characteristics define tumor-rejecting neoantigens 96%
- Deep immune profiling reveals targetable mechanisms of immune evasion in checkpoint blockade-refractory glioblastoma 96%
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%
- Microparticle-delivered Cxcl9 prolongs Braf inhibitor efficacy in melanoma 96%
- Targeting macrophages with CAR-T cells delays solid tumor progression and enhances anti-tumor immunity 96%
Similar papers in this journal
Similar papers in this journal
- IL-9 as a naturally orthogonal cytokine with optimal JAK/STAT signaling for engineered T cell therapy 95%
- Diverse priming outcomes under conditions of very rare precursor B cells 94%
- Soluble CTLA-4 mainly produced by Treg cells inhibits type 1 inflammation without hindering type 2 immunity to allow for inflammation resolution 94%
Similar papers in this journal
- Inflammatory cytokines mediate the induction of and awakening from metastatic dormancy 97%
- Cancer-cell-derived cGAMP limits the activity of tumor-associated CD8+ T cells 97%
- Neoantigen Cancer Vaccines and Different Immune Checkpoint Therapies Each Utilize Both Converging and Distinct Mechanisms that in Combination Enable Synergistic Therapeutic Efficacy 96%
"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.