Stimulation of natural killer (NK) cell and macrophage infiltration in pancreatic cancer with virulizin (V), an immunotherapeutic agent
Bibliographic record
Abstract
4257 Purpose: V is stimulates macrophages and monocytes in vitro and in vivo. Pancreatic cancer patients treated with V in phase I/II studies showed increased 6 and 12 months survival vs historical controls. V administration was associated with increased NK cell activity in patients showing the best response to V. Hence, NK cell function may be a mediator of V anti-tumor activity. Methods: To determine if V induces NK cell infiltration into tumors, CD-1 nude mice with Capan-1 pancreatic tumor xenografts were treated with V; tumor samples were analyzed by flow cytometry using NK cell-specific antibodies. Anti-tumor activity and NK cell infiltration were also evaluated in human tumor xenografts in CD-1 nude mice depleted of macrophages. Immunohistochemical staining of tumor xenografts was performed to further assess NK cell and macrophage activity. Results: V increased NK cell infiltration of tumors (59.4 – 116.0%). Macrophage depletion reduced both NK cell infiltration of tumors, and anti-tumor activity of V (P=0.1632). V-treated mice showed a significant increase in infiltration of F4/80+ (macrophages) and NK1.1+ (NK) cells, vs saline treated controls. Increased NK1.1+ cell infiltration occurred early in V treatment, and correlated with an early marker for tumor apoptosis. V treatment also resulted in a significant increase in the NK cell number in the spleen. Conclusion: Macrophage-mediated NK cell activation/recruitment is implicated in the mechanism of action of V.. These results suggest that V mediates a sustained infiltration of NK cells and macrophages into tumors. Low NK cell activity may be a risk factor for malignancy and metastases, and a negative prognostic indicator in pancreatic cancer. NK cell function and other immune activities are being assessed as biologic markers of clinical response in a Phase III trial in pancreatic cancer as a first line combination therapy with gemcitabine. NK cell function will be correlated with clinical response parameters. No significant financial relationships to disclose.
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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) | 0.001 | 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 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".