Abstract 3853: AXL inhibitor promotes anti-tumor immunity through modulation of macrophage polarization
Bibliographic record
Abstract
Abstract Polarization of tumor-associated macrophages (TAMs) to classic pro-inflammatory M1 or alternatively activated M2 types plays an important role in establishing tumor microenvironment and determining therapeutic responses. It has become increasingly clear that M2 macrophages contribute to tumor progression by producing anti-inflammatory cytokines and suppressing anti-tumor immunity. AXL receptor tyrosine kinase has recently emerged as a dual therapeutic target in oncology, due to its function in tumor growth, survival and metastasis, as well as immunosuppressive activity. AXL and its ligand Gas6 are both involved in attenuating anti-tumor immune response through modulation of TAM polarization. Thus, targeting the AXL signaling pathway is expected to promote a pro-inflammatory tumor microenvironment, in addition to direct inhibition of tumor growth. SLC-391, a selective small molecule inhibitor for AXL, displays high potency against numerous cancer cell lines through inhibition of AXL/PI3K/AKT-dependent cell proliferation and survival in vitro. Additionally, this compound was also found to alter the cytokine profile expressed in THP1-derived M2 macrophages, including upregulating pro-inflammatory CXCL10 and downregulating anti-inflammatory IL-10. Noticeably, the expression level of AXL was significantly upregulated in THP1-derived macrophages in presence of tumor cell-conditioned medium, which indicated the involvement of AXL in M2 polarization, and therefore strengthening the notion of AXL as a dual therapeutic target. In a co-culture system consisting of THP1-derived macrophages and A549 non-small cell lung cancer cells, SLC-391 targeted AXL activity in both cell types for overall tumor cell suppression through direct and macrophage-mediated inhibition. This observation is supported by inhibition of tumor growth and the increased ratio of M1/M2-polarized TAMs from mice treated with SLC-391 in a CT-26 murine colon carcinoma syngeneic model, considering CT26 cells are not sensitive to SLC-391 in cell-based proliferation assay. In summary, in addition to direct inhibition of tumor cells, SLC-391 also appears to promote anti-tumor immunity through modulation of M2 to M1 transition. Citation Format: Shenshen Lai, Qin Xu, Jun Yan, Hong Zhang, Zaihui Zhang. AXL inhibitor promotes anti-tumor immunity through modulation of macrophage polarization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3853.
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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) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".