Tissue-Resident T Cells in Liver and Lung Immune Surveillance: HBV, NK Interactions and Inhaled Mucosal Vaccines (Mala Maini)
Using liver transplant/surgical samples with paired blood, Mala Maini's group found intrahepatic tissue-resident T cell numbers correlate negatively with viral control in HBV patients, suggesting a sentinel protective role, with long-term clonal persistence validated via HLA-mismatched transplants. In a chronic HBV therapeutic vaccine model, intrahepatic NK cells constitutively upregulate PD-L1, and blocking PD-L1 with antibodies expands HBV-specific T cells in mice and patient samples. With Baletti/Stauss, they are developing TCR-redirected T cells against HBV envelope epitopes, also expressed in HBV-related liver cancer, for adoptive cell therapy. They propose inhaled vaccines targeting respiratory mucosal tissue-resident T cells for broad cross-protection against future variants or other animal coronaviruses, and stress that blood draws alone cannot capture tissue immunity.
Intrahepatic TRM: Using liver transplant/surgical samples with paired blood, found that the number of intrahepatic tissue-resident T cells is negatively correlated with viral control in HBV patients, suggesting a protective "sentinel" role in the liver, with long-lived clonal proliferative capacity (validated via HLA-mismatched transplantation).；NK–T collaboration: In a chronic HBV therapeutic vaccine model, found that intrahepatic NK cells constitutively upregulate PD-L1; antibody blockade of PD-L1 can expand HBV-specific T cells in mice and patient samples, an approach now being extended to cancer (clinical exploration of cytokine-activated NK cells).；TCR gene therapy: In collaboration with Baletti/Stauss, developing TCR-redirected T cells recognizing HBV envelope epitopes (also expressed in HBV-related liver cancer) for adoptive cell therapy.；Mucosal vaccines: Proposed using "inhaled vaccines" to target tissue-resident T cells that replicate in the respiratory mucosa, aiming to provide broad cross-protection against future variants or other animal coronaviruses (echoing the key role of T cell memory in "abortive infection" post-COVID).；Methodological insight: Emphasized that understanding immunity and monitoring immunotherapy cannot rely on blood draws alone—tissue in situ sampling must be incorporated.
- Intrahepatic TRM: Using liver transplant/surgical samples with paired blood, found that the number of intrahepatic tissue-resident T cells is negatively correlated with viral control in HBV patients, suggesting a protective "sentinel" role in the liver, with long-lived clonal proliferative capacity (validated via HLA-mismatched transplantation).
- NK–T collaboration: In a chronic HBV therapeutic vaccine model, found that intrahepatic NK cells constitutively upregulate PD-L1; antibody blockade of PD-L1 can expand HBV-specific T cells in mice and patient samples, an approach now being extended to cancer (clinical exploration of cytokine-activated NK cells).
- TCR gene therapy: In collaboration with Baletti/Stauss, developing TCR-redirected T cells recognizing HBV envelope epitopes (also expressed in HBV-related liver cancer) for adoptive cell therapy.
- Mucosal vaccines: Proposed using "inhaled vaccines" to target tissue-resident T cells that replicate in the respiratory mucosa, aiming to provide broad cross-protection against future variants or other animal coronaviruses (echoing the key role of T cell memory in "abortive infection" post-COVID).
- Methodological insight: Emphasized that understanding immunity and monitoring immunotherapy cannot rely on blood draws alone—tissue in situ sampling must be incorporated.
Covers multiple studies on tissue-resident T cell immunity in HBV and mucosal vaccine design.
Source: YouTube