FLT3L combined with GM-CSF induced dendritic cells drive broad tumor-specific CD8+ T cell responses and remodel the tumor microenvironment to enhance anti-tumor efficacy
Bibliographic record
Abstract
Background Dendritic cells (DCs) play a crucial role in anti-tumor immunity by capturing, processing, and presenting tumor antigens to T cells, making DC-based immunotherapy a promising approach for cancer treatment. However, the most commonly used clinical strategy still relies on inducing DCs in vitro using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL - 4) (GM/IL4-DCs), which often results in a heterogeneous cell population with suboptimal anti-tumor function. Here, we compared DCs generated by co-stimulating with FMS-like tyrosine kinase 3 ligand (FLT3L) and GM-CSF (FL/GM-DCs) with the conventional GM/IL4-DCs. Method To compare the functional differences of DCs induced by different methods, we conducted a comprehensive study. Mouse bone marrow cells were continuously cultured for 9 days in a FLT3L/GM-CSF-containing medium. After cell collection, we analyzed the composition, subpopulations, and status of FL/GM-DCs using flow cytometry and scRNA-seq. Flow cytometry was also used to assess their antigen presentation and ability to stimulate T cells. In vivo experiments were performed to examine their distribution, anti-tumor effects, and therapeutic responses in tumor models. Finally, combining scRNA-seq and scTCR-seq, we explored the mechanisms by which FL/GM-DCs reshape the tumor microenvironment. Results The results showed that FL/GM-DCs exhibited a unique subpopulation distribution, characterized by an abundance of conventional cDC subpopulations, and demonstrated enhanced cross-antigen presentation capabilities. Notably, FL/GM-DCs were able to induce a broader and more tumor-specific CD8+ T cell response, effectively reshaping the tumor microenvironment by promoting the infiltration of cytotoxic T lymphocytes (CTLs) and reducing immunosuppressive components. In contrast, GM/IL4-DCs contained fewer cDC subpopulations, eliciting a weaker initial CD8+ T cell response and yielding relatively inferior anti-tumor effects. Conclusion In summary, FLT3L combined with GM-CSF induced DCs, through their unique subpopulation composition and functional state, can more effectively expand tumor-specific CD8+ T cells and reshape the tumor microenvironment, thereby achieving superior immunotherapy outcomes. This study highlights the potential of FL/GM-DCs as a next-generation DC platform, paving the way for improved clinical translation of DC-based adoptive cancer immunotherapies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".