Author response: Tumor initiating cells induce Cxcr4-mediated infiltration of pro-tumoral macrophages into the brain
Bibliographic record
Abstract
Brain tumors can be aggressive, difficult to treat and are often incurable. Removing brain tumors by surgery can be challenging because the tumor cells infiltrate into the healthy tissue. Brain tumors grow in close physical contact with other cells, such as cells of the immune system. This includes cells called macrophages and microglia, which normally defend us against injuries and infections. However, instead of acting against the tumor as one might expect, macrophages and microglia actually support the growth of brain tumors. It is not clear how and when during the development of a brain tumor the macrophages and microglia start helping the tumor cells to grow. Previous studies in this area have focused on these cell types found in advance brain tumors. Chia et al. have now looked at the earliest stages of tumor development, monitoring how macrophages and microglia respond to cancer cells. To mimic human brain tumors, Chia et al. expressed a cancer-promoting version of a human protein in nerve cells of zebrafish larvae. These cells started behaving like early tumor cells. Live microscopy revealed that the tumor cells attract macrophages and microglia into their area, and that they also activate the immune cells. Biochemical experiments showed that the early tumor cells make and release a protein called Sdf1. Macrophages and microglia sense Sdf1 in the environment with a protein called Cxcr4 on their cell surfaces. When the gene for Cxcr4 was deleted in the zebrafish, the macrophages and microglia were not recruited into the developing tumors. When macrophages and microglia were depleted from the zebrafish larvae, the nerve cells with the mutant protein grew less well, supporting the idea that the immune cells enhance the development of early tumors. A better understanding of how tumor cells and immune cells interact in the brain may help in the search for new anti-cancer drugs. Furthermore, the way in which macrophages and microglia are recruited to the tumor cells could be similar when tumors return after treatment. Future studies will test this hypothesis and, if it proves true, interfering with the macrophage and microglia response might delay the relapse of tumors.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.150 | 0.051 |
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".