A novel type-2 innate lymphoid cell-based immunotherapy for cancer
Bibliographic record
Abstract
Cell-based cancer immunotherapy has achieved significant advancements, providing a source of hope for cancer patients. Notwithstanding the considerable progress in cell-based immunotherapy, the persistently low response rates and the exorbitant costs associated with their implementation still present a formidable challenge in clinical settings. In the landscape of cell-based cancer immunotherapies, an uncharted territory involves Type 2 innate lymphoid cells (ILC2s) and interleukin-33 (IL-33) which promotes ILC2 functionality, recognized for their inherent ability to enhance immune responses. Recent discoveries regarding their role in actuating cytolytic T lymphocyte responses, including curbing tumor growth rates and hindering metastasis, have added a new dimension to our understanding of the IL-33/ILC2 axis. These recent insights may hold significant promise for ILC2 cell-based immunotherapy. Nevertheless, the prospect of adoptively transferring ILC2s to confer immune protection against tumors has yet to be investigated. The present study addresses this hypothesis, revealing that ILC2s isolated from the lungs of tumor-bearing mice, and tumor infiltrating ILC2s when adoptively transferred after tumor establishment at a ratio of one ILC2 per sixty tumor cells, leads to an influx of tumor infiltrating CD4+ and CD8+ T lymphocytes as well as tumor infiltrating eosinophils resulting in a remarkable reduction in tumor growth. Moreover, we find that post-adoptive transfer of ILC2s, the number of tumor infiltrating ILC2s is inversely proportional to tumor size. Finally, we find corollaries of the IL-33/ILC2 axis enhancing the infiltration of eosinophils in human prostate carcinomas patients' expressing high levels of IL-33 versus those expressing low levels of IL-33. Our results underscore the heightened efficacy of adoptively transferred ILC2s compared to alternative approaches, revealing an approximately one hundred fifty-fold superiority on a cell-per-cell basis over CAR T-cells in the specific targeting and elimination of tumors within the same experimental model. Overall, this study demonstrates the functional significance of ILC2s in cancer immunosurveillance and provides the proof of concept of the potential utility of ILC2 cell-based cancer immunotherapies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".