Tissue-resident memory T cells (T RM ) can be induced by infection and vaccination, and play a key role in maintaining long-term protective immunity against mucosal pathogens. Our studies explored the key factors and mechanisms affecting the differentiation, maturation, and stable residence of gastric epithelial CD4 + T RM induced by Helicobacter pylori (Hp) vaccine and optimized Hp vaccination to promote the generation and residence of T RM .CD38 regulated mitochondrial activity and enhanced TGF-β signal transduction to promote the differentiation and residence of gastric epithelial CD4 + T RM by mediating the expression of CD105. Extracellular nucleotides influenced the long-term maintenance of T RM in gastric epithelium by P2RX7. Vitamin D3 and Gram-positive enhancer matrix particles (GEMs)as immune adjuvants combined with Hp vaccination promoted the production of CD69 + CD103 + CD4 + T RM .
Background T cell-based immunotherapies are facing great challenges in the recruitment and activation of tumor-specific T cells against solid tumors. Among which, utilizing nanobody (Nb) or nanobodies (Nbs) to construct T cell engager has emerged as a more practical potential for enhancing the anti-tumor effectiveness of T cells. Here, we designed a new Nb-guided multifunctional T cell engager (Nb-MuTE) that not only recruited effector T cells into the tumor tissues, but also efficiently activated T cells anti-tumor immunity when synergies with photothermal effect. Results The Nb-MuTE, which was constructed based on an indocyanine green (ICG)-containing liposome with surface conjugation of CD105 and CD3 Nbs, and showed excellent targetability to both tumor and T cells, following enhancement of activation, proliferation and cytokine secretion of tumor-specific T cells. Notably, the immunological anti-tumor functions of Nb-MuTE-mediated T cells were further enhanced by the ICG-induced photothermal effect in vitro and in vivo. Conclusions Such a new platform Nb-MuTE provides a practical and “all-in-one” strategy to potentiate T cell responses for the treatment of solid tumor in clinic.
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