Essential Role of <scp>NLRC5</scp> in Cancer Immune Surveillance and Cancer Immunoediting
Bibliographic record
Abstract
ABSTRACT A key mechanism of tumour immune escape from CD8 + cytotoxic T lymphocytes occurs via downregulation of NLRC5, an IFNγ‐induced transcriptional activator of MHC class‐I. As NLRC5 deficiency does not abrogate CD8 + T cell development, we investigated whether NLRC5‐dependent antitumour immune mechanisms are required for immune surveillance. We studied the development of 3‐methylcholanthrene (MCA)‐induced endogenous fibrosarcoma in Nlrc5 −/− mice with Nlrc5 +/+ and Rag1 −/− mice serving as controls. Nlrc5 −/− and Rag1 −/− mice showed increased propensity to develop MCA‐induced tumours with a higher growth rate compared to Nlrc5 +/+ mice and displayed significantly reduced survival. Tumours from Nlrc5 +/+ and Nlrc5 −/− mice, but not from Rag1 −/− mice, contained necrotic areas and displayed T cell infiltration. Tumour cell lines established from MCA‐induced tumours were evaluated for their sensitivity to immune‐mediated growth control following implantation into immunocompetent C57BL/6 and immunodeficient Rag1 −/− hosts. Tumours formed by Nlrc5 +/+ tumour cell lines progressed unhindered in C57BL/6 hosts that reflected their immunoedited status, whereas cell lines from Nlrc5 −/− and Rag1 −/− tumours were efficiently controlled, indicating their non‐immunoedited status. Proteomic analysis by mass spectrometry followed by pathway analysis revealed enrichment of granzyme‐mediated cytolytic pathway in Nlrc5 +/+ tumours that were absent in Nlrc5 −/− tumours, which showed enrichment of humoral and innate immune pathways. Overall, our findings show that NLRC5 is required for robust tumour immune surveillance and tumour immunoediting and that compensatory humoral and innate immune mechanisms activated by the loss of NLRC5 are insufficient for cancer immune surveillance and cancer immunoediting.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.000 | 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".