PWE-152 Selective Loss of Oncofoetal Antigen 5T4-Specific T Cell Response Correlates with Progression of Colorectal Cancer
Bibliographic record
Abstract
Introduction The human oncofoetal antigen 5T4 is expressed on many human carcinomas, including colorectal cancer (CRC) cells, but has limited expression on normal tissues making it an ideal target for cancer immunotherapy. Here, a significant loss of T cell response to 5T4 in patients with more advanced CRC has been identified. Methods Lymphocyte samples obtained from HLA-typed CRC patients and healthy donor controls were cultured for two weeks with pools of overlapping 20mer 5T4 peptides, spanning the entire protein, before subsequent analysis for antigen specificity, as measured by the highly sensitive IFN-g/IL-10 ELISPOT assay. Results Positive 5T4-specific lines were identified in 79% (15/19) of CRC patients and all (11/11) healthy donors tested. Intriguingly, CRC patients respond to significantly fewer candidate epitopes and generate a lower magnitude of IFN-γ responses to 5T4. Furthermore this response diminishes with tumour advancement despite similar responses to the recall antigen PPD. The mechanism of loss of T cell response is independent of HLA-DR type or patient age, but depletion experiments indicate suppression by Foxp3+ regulatory CD4+ T cells. In addition, analysis of peripheral blood and tumour-infiltrating lymphocytes in the same cohort of patients revealed a marked suppressive phenotype in comparison to healthy age-matched controls. Conclusion Effective anti-tumour immunotherapy will be reliant upon overcoming such regulation of tumour-specific T cell responses. These data support a rationale for re-stimulating 5T4-specific immune responses in CRC patients, and reducing tumour-induced immunosuppression to enhance immunotherapy. Disclosure of Interest None Declared.
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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) | 0.003 | 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".