The beauty of TLR agonists for CTCL.

摘要

Importantly, the study of Kim and colleagues in this issue of Blood demonstrates that in situ vaccination of skin lesions of cutaneous T-cell lymphoma (CTCL) patients with subtherapeutic doses of the TLR9 agonist CpG oligodeoxynucleotides (ODNs) simultaneously with localized lesional radiation can lead to regression of distant, untreated clinical lesions. These results suggest that local radiation may render the malignant T-cell antigens more available for processing by antigen-presenting cells and that the priming of TLR9-bearing plasmacytoid dendritic cells (pDCs) by CpG-ODNs, even at subtherapeutic doses, appears to be adequate for the en-hancement of processing of released tumor antigen leading to the generation of an anti-tumor response. The immunologic effects of this approach were evident on histologic examination of regressing lesions that demonstrated a decline in numbers of CD25~+/Foxp3~+ regulatory T cells along with an accompanying significant increase in pDCs. There was no change in these cellular populations within lesions of patients who had no response. Although the 6-mg dose of the CpG used in this study was previously demonstrated in a phase 1 trial to be subtherapeutic, it appears that the DC priming effect was nevertheless adequate to produce responses with the multimodality approach employed here.