Abstract PO-084: Deletion of macrophage migration inhibitory factor promotes antitumoral T cell infiltration and inhibits MDSC recruitment to the head and neck cancer microenvironment
Why this work is in the frame
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Bibliographic record
Abstract
Abstract Head and neck squamous cell carcinoma (HNSCC) is a significant public health concern worldwide. Immunomodulatory targets in the HNSCC tumor microenvironment are crucial to enhance the efficacy of HNSCC immunotherapy. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that has been linked to worse prognosis in many cancers, but the mechanistic role of MIF in HNSCC remains unclear. Using a murine orthotopic oral cancer model in Mif+/+ or Mif− / − mice, we determined the function of host derived MIF in HNSCC tumor development, metastasis as well as localized and systemic tumor immune responses. We found that Mif− / − mice have decreased tumor growth and burden compared to their wild-type counterparts. Flow cytometric analysis of immune populations within the primary tumor site revealed increased T cell recruitment to the HNSCC tumor microenvironment, within the tumors of Mif− / − mice. MIF deletion also enhanced the effector function of anti-tumoral Th1 cells and decreased the accumulation of granulocytic MDSC in the tumor microenvironment. Furthermore, we show that isolated MDSC chemotactically respond to MIF in a dose dependent manner which is inhibited when MIF is depleted. Interestingly, MDSCs of tumor bearing Mif− / − mice expressed increased levels of PDL1 compared to Mif+/+ mice. However, Mif− / − and Mif+/+ MDSCs have comparable abilities to suppress T cell proliferation. Herein we describe a chemotactic and immunomodulatory role for MIF in the context of HNSCC. MIF targeted immunomodulation remains a potentially viable cancer therapeutic, however more remains to be understood about the cellular interaction of MIF within the tumor microenvironment before these targeted therapies can be effectively employed Citation Format: Steve Oghumu. Deletion of macrophage migration inhibitory factor promotes antitumoral T cell infiltration and inhibits MDSC recruitment to the head and neck cancer microenvironment [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-084.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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 it