![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB |
Preview |
PDF (Supplementary Materials)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
680kB |
| Item Type: | Article |
|---|---|
| Title: | CD8(+) T cell-derived CD40L mediates noncanonical cytotoxicity in CD40-expressing cancer cells |
| Creators: |
Schiele, P., Sada Japp, A.  ORCID: https://orcid.org/0000-0001-8106-8987, Stark, R., Sattelberg, J.J., Nikolaou, C., Kornhuber, G., Abbasi, P., Ding, N., Rosnev, S., Meinke, S., Mühle, K., Loyal, L., Braun, J., Dingeldey, M., Durlanik, S., Matzmohr, N., Ponikwicka-Tyszko, D., Wolczynski, S., Rahman, N.A., Taniuchi, I., Schlickeiser, S., Giesecke-Thiel, C., Blankenstein, T. ORCID: https://orcid.org/0000-0002-3357-4321, Na, I.K. ORCID: https://orcid.org/0000-0001-9902-5424, Thiel, A. and Frentsch, M.
|
| Abstract: | T cells and their effector functions, in particular the canonical cytotoxicity of CD8(+) T cells involving perforin, granzymes, Fas ligand (FasL), and tumor necrosis factor related apoptosis inducing ligand (TRAIL), are crucial for tumor immunity. Here, we reveal a previously unidentified mechanism by which CD40L-expressing CD8(+) T cells induce cytotoxicity in cancer cells. In murine models, up to 50% of tumor-specific CD8(+) T cells expressed CD40L, and conditional CD40L ablation in CD8(+) T cells alone led to tumor formation. Mechanistically, CD40L(+)CD8(+) T cells can induce cell death in CD40-expressing cancer cells by triggering caspase-8 activation. We demonstrate that a gene signature for resistance to CD40 signaling-induced cell death strongly correlates with worse survival in different human cancer cohorts. Our results introduce CD40L as a rather counterintuitive, noncanonical cytotoxic factor that complements the capabilities of CD8(+) T cells to combat cancers and has the potential to enhance the efficacy of immunotherapies. |
| Keywords: | CD40 Antigens, CD40 Ligand, CD8-Positive T-Lymphocytes, Caspase 8, Immunologic Cytotoxicity, Neoplasms, Signal Transduction, Tumor Cell Line, Animals, Mice |
| Source: | Science Advances |
| ISSN: | 2375-2548 |
| Publisher: | American Association for the Advancement of Science |
| Volume: | 11 |
| Number: | 21 |
| Page Range: | eadr9331 |
| Date: | 23 May 2025 |
| Official Publication: | https://doi.org/10.1126/sciadv.adr9331 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
