Spontaneous murine mammary tumours demonstrate a range of sensitivities to adoptively transferred T cells: defining the molecular and histological determinants of regression versus progression
Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 47, 2006 1164 To investigate T cell responses to spontaneous mammary tumours and define mechanisms of immune evasion, we developed a novel transgenic mouse model involving spontaneously arising, epitope-tagged mammary tumours. CD8+ and CD4+ T cell epitopes from ovalbumin were added to the C-terminus of the HER2/ neu oncogene to enable recognition by T cell receptor transgenic CD8+ (OT-I) and CD4+ (OT-II) T cells. C57Bl/6 transgenic mice expressing neu OTI/OTII in mammary epithelium together with a dominant-negative p53 transgene (DN p53 ) develop spontaneous mammary carcinomas at 6-10 months of age. T cell responses to these tumours were studied by adoptive transfer of naive OT-I and/or OT-II T cells into tumour-bearing mice. In mice that received OT-II cells, minimal or no T cell proliferation was observed in response to neu OTI/OTII-expressing tumours, even as late as 13 days post transfer. By contrast, OT-I T cells, infused alone or with OT-II T cells, proliferated vigorously within 3 days of adoptive transfer and subsequently infiltrated ∼75% of tumours by day 6 where they formed the major constituent (∼74%, n=8) of the CD8+ immune infiltrate. This resulted in complete regression of 19% (11/59) of tumours, with the remaining tumours showing partial regression (25%), stabilized growth (15%) or progressive disease (41%). Intriguingly, many non-regressing tumours continued to express neu OTI/OTII yet showed greatly reduced lymphocytic infiltrates at later time points (> day 11). Similarly, tumours generated from cell lines of progressive tumours failed to become infiltrated by OT-I or OT-II cells, suggesting they developed mechanisms to physically exclude T cells. To our knowledge, this is the first demonstration of CD8+ T cells eradicating established, spontaneously generated mammary tumours. We are currently investigating the mechanism(s) by which progressive tumours impair the infiltration and/or function of CD8+ T cells, and whether this can be reversed by combining adoptive T cell therapy with other treatments, such as chemotherapy, that disrupt tumour architecture.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".