AI Article Synopsis
- Inducing tertiary lymphoid structures (TLS) can enhance the immune response against tumors, and mouse models are essential for studying TLS formation strategies.
- Oncolytic herpes simplex virus-1 (oHSV) shows potential in promoting TLS development by increasing the presence of B cells and specific T cells, suggesting its role in antitumor immunity.
- The study highlights that oHSV enhances TLS formation via the CXCL10/CXCR3 pathway, and this effect improves survival rates when combined with αPD-1 treatment, paving the way for future cancer immunotherapy strategies.
Article Abstract
Inducing tertiary lymphoid structure (TLS) formation can fuel antitumor immunity. It is necessary to create mouse models containing TLS to explore strategies of TLS formation. Oncolytic herpes simplex virus-1 (oHSV) exhibited intense effects in preclinical and clinical trials. However, the role of oHSV in TLS formation remains to be elucidated. Here, we observed the presence of TLS in 4MOSC1 and MC38 subcutaneous tumour models. Interestingly, oHSV evoked TLS formation, and increased infiltration of B cells and stem-like TCF1CD8 T cells proliferation. Mechanistically, oHSV increased the expression of TLS-related chemokines, along with upregulated CXCL10/CXCR3 to facilitate TLS formation. Notably, CXCL10 and CXCR3 were favourable prognostic factors for cancer patients, and closely related with immune cells infiltration. Inhibiting CXCL10/CXCR3 reduced TCF1CD8 T cells and granzyme B expression, and impaired oHSV-mediated TLS formation. Furthermore, oHSV-mediated TLS formation revealed superior response and survival rate when combined with αPD-1 treatment. Collectively, these findings indicate that oHSV recruits stem-like TCF1CD8 T cells through CXCL10/CXCR3 pathway to propagate TLS formation, and warrants future antitumor immunity development.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693575 | PMC |
| http://dx.doi.org/10.1111/cpr.13740 | DOI Listing |
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