Rapid expansion of M-MDSCs and association with high levels of plasma TSLP and primary resistance to PD-1 inhibitors in metastatic NSCLC.
Bibliographic record
Abstract
3084 Background: Elevated frequency of peripheral myeloid cell populations has consistently been associated with poor response to immune checkpoint inhibitors (ICI) in metastatic non-small cell lung cancer (mNSCLC). The mechanisms underlying this relationship remains poorly understood. Thymic stromal lymphopoietin (TSLP), a cytokine involved in T-cell maturation, has been implicated in a complex feedback loop leading to tumor growth and expansion of myeloid populations. We hypothesized that TSLP levels directly correlate with the presence and expansion of myeloid derived suppressor cell (MDSC) populations and sought to explore their association with response to PD-1 inhibitors in mNSCLC. Methods: mNSCLC patients treated with ICIs underwent baseline and serial blood collection. Peripheral blood mononuclear cells (PBMC) were analyzed by high-dimensional flow cytometry using validated panels to evaluate T/B/NK-cell, Treg and myeloid populations. Plasma cytokines including TSLP were analyzed using ELISA and Luminex assays. Cox and logistic regressions were utilized to correlate biomarkers with progression-free survival (PFS), overall survival (OS) and radiographic response. Results: 30 mNSCLC patients treated with single-agent ICI were included in the analysis. TSLP level was significantly associated with expansion of monocytic(M)-MDSCs in response to ICI treatment (p=0.02). M-MDSC frequency after a median of 20 days of ICI treatment was significantly associated with progressive disease (PD), reduced PFS and OS (all p<0.05) whereas no correlation was seen with baseline M-MDSC frequency. Patients with a doubling of M-MDSCs (n=11) after treatment had a primary PD rate of 64% vs 24% (OR 7.0, p=0.04) and significantly worse median PFS (2.5 vs 7.8 months, HR 2.6 p=0.04). Conclusions: Early expansion of circulating M-MDSCs after treatment with PD-1 inhibitors is associated with elevated baseline TSLP levels and primary disease progression following ICI therapy in mNSCLC. These findings suggest that elevated TSLP and early expansion of myeloid populations may represent an important mechanism of primary resistance to PD-1 inhibitors in mNSCLC.
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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".