TrendInduction of TH1 and TH2 responses: a key role for the ‘natural’ immune response?
Abstract
What pushes a T-cell response towards a predominantly TH1 or TH2 phenotype? Several factors have been proposed, including the properties of antigens, dose of antigen, site of exposure and ongoing immune response in the host. Here, Sergio Romagnani presents new evidence to indicate a determining role for the ‘natural’ immune response, including NK cells and cells of the mast cell/basophil lineage, in the subsequent ‘specific’ T-cell response.
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Ibrutinib (IBR), an irreversible Bruton’s tyrosine kinase (BTK) inhibitor, is expected to be a potent therapeutic modality, given that BTK is overexpressed in tumor-associated macrophages (TAMs) and participates in promoting tumor progression, angiogenesis, and immunosuppression. However, rapid clearance in vivo and low tumor accumulation have rendered effective uptake of IBR by TAMs challenge. Herein, we designed and synthesized a sialic acid (SA)–stearic acid conjugate modified on the surface of nanocomplexes to encapsulate IBR (SA/IBR/EPG) for targeted delivery of IBR to TAMs. The developed SA/IBR/EPG nanocomplexes exhibited high efficiency in targeting TAMs and inhibiting BTK activation, consequently inhibiting Th2 tumorigenic cytokine release, reducing angiogenesis, and suppressing tumor growth. These results implied that the SA/IBR/EPG nanocomplex could be a promising strategy for TAM-targeting immunotherapy with minimal systemic side effects.
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