PWE-006 Differential immune responses between proximal and distal colorectal cancer
Bibliographic record
Abstract
Introduction Colorectal cancer (CRC) is a major cause of mortality. Dendritic cells (DC) promote tumour immunity or tolerance dictated by tissue microenvironment. Proximal colon (right-sided) CRC has lower incidence but poorer prognosis than distal colon (left-sided) CRC. This may be due to immunological differences between the proximal and distal colon. However, cellular and molecular studies on these differences especially in CRC are scarce. We aimed to characterise the immune activity in both compartments. Method Activation and migration of DC from human mucosal and tumour biopsies in health and CRC were investigated using flow-cytometry, immunohistology. Functional studies were performed using migration assay techniques. E-Cadherin, a tumour dissemination inhibitor was determined by real time PCR in a separate group of tumours from anaemic CRC patient. Results Co-stimulatory molecules (CD40/CD86) were expressed on more DC from proximal than distal colon in health and CRC (p=0.03; p=0.01 respectively). In CRC, DC from proximal mucosa and tumour showed increased skin-homing (CLA) and ILT3 (marker for immature DC) indicating reduced potential to focus immune activity to this compartment (p=0.03; p=0.01 respectively). CRC-DC showed increased CCR7 (lymph node homing) with greater migration but with negative correlation with tumour size. E-Cadherin mRNA fold-change was significantly lower on proximal tumour cells compared with those in the distal compartment. Functional studies using supernatants from normal mucosae or tumours reproduced the above changes in CRC-DC; changes thus reflected changed gut micro-environment in CRC. Conclusion Higher immune activity, in proximal colon, may underlie lower tumour incidence but higher tumour aggression due to tumour evolution in immunologically active microenvironment. This may have an impact on colorectal cancer treatment, for example, optimisation of current therapies based on the anatomical site of the colorectal tumour. Hence, establishment of standardised management for colon cancer by tumour location is needed. Reference . Bernardo D, et al., Chemokine (C-C Motif) Receptor2 Mediates Dendritic Cell Recruitment to the Human Colon but Is Not Responsible for Differences Observed in Dendritic Cell Subsets, Phenotype, and Function Between the Proximal and Distal Colon. Cell Mol Gastroenterol Hepatol2016;2(1):22–39. 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) | 0.012 | 0.002 |
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".