CD8+ T cell-derived CD40L mediates non-canonical cytotoxicity in CD40-expressing cancer cells
Data files
May 07, 2025 version files 10.55 MB
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Expression_22Q1_RCC.csv
10.55 MB
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RCC_Info.csv
576 B
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README.md
1.80 KB
Abstract
T cells and their effector functions, in particular the canonical cytotoxicity of CD8+ T cells involving perforin, granzymes, Fas Ligand, and 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 counter-intuitive, non-canonical cytotoxic factor that complements the capabilities of CD8+ T cells to combat cancers and has the potential to enhance the efficacy of immunotherapies.
https://doi.org/10.5061/dryad.8sf7m0d12
Description of the data and file structure
These files contain the R scripts and the data used for the analysis:
R codes
- Figure 7C: Heatmap_Fig_7c.R
- Figure 7D: Survival_Fig_7d.R
- Figure 7E: Partial_Cor_TCGA_Fig_7e.R
- Figure 7F: Survival_Checkmate_Fig_7f.R
- Figure S8: Stage_Cor_TCGA_Fig_S8.R
- Figure S9: Partial_Cor_Checkmate_Fig_S9.R
data files
Expression_22Q1_RCC.csv - contains the expression data of the renal cell carcinoma (RCC) lines downloaded from the Encyclopaedia of Cancer Cell Lines. In the table each row represents an individual patient, each column a Gene. The values in the table represent gene expression TPM values of the protein coding genes for the cell lines. Values are inferred from RNA-seq data using RSEM (stranded or unstranded mode, depending on each sample's sequencing protocol) and are reported after log2 transformation, using a pseudo-count of 1; log2(TPM+1).
RCC_Info.csv - include the response data to CD40 signaling in RCC lines. RCC_Info.csv - include the response data to CD40 signaling in RCC lines. The names of the cell lines are listed in the first column under cell lines, in the second column the tumor entity under indication in the third column the response of the cell lines to CD40-mediated cytotoxicity under reaction, with a death rate of less than 5% categorized as resistant (Res) and more than 5% as sensitive (Sens). Untested cell lines were categorized as unknown (Unk).
Data from the Checkmate studies were taken from the following manuscript https://doi.org/10.1038/s41591-020-0839-y