MHC-II-restricted neoantigen vaccine reverses immune microenvironment and overcomes resistance to immune-checkpoint inhibitors in cold tumors.
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[BACKGROUND] Cold tumors, characterized by poor T cell infiltration and an immunosuppressive tumor microenvironment (TME), are generally resistant to immune-checkpoint inhibitors (ICIs).
APA
Song X, Lu C, et al. (2026). MHC-II-restricted neoantigen vaccine reverses immune microenvironment and overcomes resistance to immune-checkpoint inhibitors in cold tumors.. Med (New York, N.Y.), 7(1), 100936. https://doi.org/10.1016/j.medj.2025.100936
MLA
Song X, et al.. "MHC-II-restricted neoantigen vaccine reverses immune microenvironment and overcomes resistance to immune-checkpoint inhibitors in cold tumors.." Med (New York, N.Y.), vol. 7, no. 1, 2026, pp. 100936.
PMID
41308654 ↗
Abstract 한글 요약
[BACKGROUND] Cold tumors, characterized by poor T cell infiltration and an immunosuppressive tumor microenvironment (TME), are generally resistant to immune-checkpoint inhibitors (ICIs). Although CD4 T cells play a critical role in anti-tumor immunity, it remains unclear whether major histocompatibility complex (MHC)-II-restricted neoantigen vaccines can reprogram the immunosuppressive TME and overcome ICI resistance.
[METHODS] Using the B16F10 model, we evaluated the MHC-II-restricted vaccine efficacy, profiled immune responses via flow cytometry and single-cell RNA sequencing, and identified the potential combination therapy targets poliovirus receptor (PVR) via NicheNet analysis. The combined efficacy was then validated in vitro and in vivo.
[FINDINGS] MHC-II-restricted neoantigen vaccine promoted inflammatory signaling within the TME and enhanced infiltration of CD4 and CD8 T cells, along with increased interferon (IFN)-γ production and signs of T cell exhaustion, which provided a prerequisite for ICI response. NicheNet analysis revealed enrichment of the inhibitory immune-checkpoint axis PVR-T cell immunoglobulin and ITIM domain (TIGIT) following vaccination. The combination of the vaccines and TIGIT blockade exhibited synergistic anti-tumor efficacy. This combination enhanced cytokine production by antigen-specific T cells, promoted effector memory differentiation, and delayed exhaustion of CD8 T cells.
[CONCLUSIONS] MHC-II-restricted neoantigen vaccine remodels the immune inhibitory TME with insufficient T cell infiltration and synergizes with TIGIT blockade to suppress tumor growth, providing a promising combinatorial strategy for cold tumors.
[FUNDING] Supported by the National Key Research and Development Program of China (2023YFC2506400), the National Natural Science Foundation (82373263), and the Fundamental Research Funds for the Central Universities (0214-14380506).
[METHODS] Using the B16F10 model, we evaluated the MHC-II-restricted vaccine efficacy, profiled immune responses via flow cytometry and single-cell RNA sequencing, and identified the potential combination therapy targets poliovirus receptor (PVR) via NicheNet analysis. The combined efficacy was then validated in vitro and in vivo.
[FINDINGS] MHC-II-restricted neoantigen vaccine promoted inflammatory signaling within the TME and enhanced infiltration of CD4 and CD8 T cells, along with increased interferon (IFN)-γ production and signs of T cell exhaustion, which provided a prerequisite for ICI response. NicheNet analysis revealed enrichment of the inhibitory immune-checkpoint axis PVR-T cell immunoglobulin and ITIM domain (TIGIT) following vaccination. The combination of the vaccines and TIGIT blockade exhibited synergistic anti-tumor efficacy. This combination enhanced cytokine production by antigen-specific T cells, promoted effector memory differentiation, and delayed exhaustion of CD8 T cells.
[CONCLUSIONS] MHC-II-restricted neoantigen vaccine remodels the immune inhibitory TME with insufficient T cell infiltration and synergizes with TIGIT blockade to suppress tumor growth, providing a promising combinatorial strategy for cold tumors.
[FUNDING] Supported by the National Key Research and Development Program of China (2023YFC2506400), the National Natural Science Foundation (82373263), and the Fundamental Research Funds for the Central Universities (0214-14380506).
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Tumor Microenvironment
- Cancer Vaccines
- Animals
- Immune Checkpoint Inhibitors
- Mice
- Inbred C57BL
- CD8-Positive T-Lymphocytes
- Antigens
- Neoplasm
- CD4-Positive T-Lymphocytes
- Drug Resistance
- Histocompatibility Antigens Class II
- Female
- Receptors
- Virus
- MHC-II-restricted neoantigen vaccines
- Pre-clinical research
- TIGIT antibody
- cold tumor
- immune-checkpoint inhibitor
- tumor microenvironment
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