Abstract 447: Hypoxia induces tumor cell escape from T cell-mediated immunity via up-regulation of B7-H1.
Bibliographic record
Abstract
Abstract In the current research we describe a novel mechanism by which hypoxia contributes to tumour cell escape from lysis mediated by cytotoxic T lymphocytes (CTLs). Specifically, we show that when exposed to hypoxia for 24 h, human DU145 prostate and MDA-MB-231 breast cancer cells, as well as mouse B16-OVA melanoma cells, increased their expression of the immune inhibitory ligand B7-H1 at both the mRNA and protein levels in a manner dependent on hypoxia-inducible factor-1α (HIF-1α). Moreover, our findings revealed that the hypoxia-induced up-regulation of B7-H1 expression in tumour cells resulted in increased tumour cell resistance to lysis mediated by primed CTLs. We previously demonstrated that activation of nitric oxide (NO) signalling blocks HIF-1α accumulation in tumour cells exposed to hypoxia. Here we show that the NO mimetic glyceryl trinitrate (GTN; 10 nM) prevented the hypoxia-induced up-regulation of tumour cell B7-H1 expression as well as the increased resistance to CTL-mediated lysis. Furthermore, co-culture studies revealed that the increased expression of B7-H1 following exposure of tumour cells to hypoxia led to the apoptotic death of CTLs as well as Jurkat leukemia cells in a manner that could be prevented by blocking B7-H1, programmed cell death-1 receptor (B7-H1 receptor expressed by T cells) or by incubation with low concentrations of GTN. These results indicate that a potential immunotherapy of cancer could involve interference with B7-H1 function in hypoxic tumour cells via administration of NO mimetics. Citation Format: Ivraym B. Barsoum, Chelsea A. Smallwood, D. Robert Siemens, Charles H. Graham. Hypoxia induces tumor cell escape from T cell-mediated immunity via up-regulation of B7-H1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 447. doi:10.1158/1538-7445.AM2013-447
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".