Abstract B039: T cell recruitment dynamics at different stages of primary and metastatic colorectal cancer
Bibliographic record
Abstract
Abstract Colorectal cancer (CRC) is the fourth deadliest cancer worldwide, primarily due to metastasis. The current standard therapy for patients with CRC includes neoadjuvant therapies combined with surgery, often resulting in severe complications that affect patients’ lifestyles. Hence, there is a critical need to improve our understanding of the tumor microenvironment to improve the current therapeutics for metastatic CRC. We characterized T cell dynamics in response to tumors at early (1-2 weeks) versus late stages (6-7 weeks) of CRC development in different colon compartments (tumor, epithelium, lamina propria), as well as in colon-draining lymph nodes and the liver as potential metastasis sites. To achieve this, we injected by colonoscopy tumor AKP mouse organoids (mutations in APC, Kras, and P53 genes) or metastatic AKP mouse organoids in the colon walls of a novel fate-mapping strain (iSell-tomato). This model allows for the labelling of peripheral T cells that are recruited to the tissue or tumor sites. Our initial data showed an enhanced recruitment of CD4 and CD8ab T cells to the colon epithelium in early stage AKP (non-metastatic) tumor models compared to late-stage AKP and metastatic-AKP models at both stages. These recruited cells exhibited an enhanced anti-tumorigenic profile characterized by the production of IFNg and reduced frequency of FoxP3+ CD4 regulatory T cells (Tregs). In contrast, T cells recruited to early stage metastatic-AKP tumors and late-stage tumors of the colon and liver exhibited enhanced exhaustion characterized by an increased frequency of PD1+ CD4 and CD8ab T cells. These data suggest a time- and aggressiveness-dependent effect of tumors on immune cell infiltrates that, in turn, affect tumor progression and metastasis. Citation Format: Marwa A Saad, Angelina Bilate, Daniel Mucida. T cell recruitment dynamics at different stages of primary and metastatic colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr B039.
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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 | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".