TCR clonality and Treg frequency as predictors of outcome in stage III NSCLC treated with durvalumab.
Bibliographic record
Abstract
3050 Background: Novel blood-based biomarkers evaluating T-cell receptor (TCR) clonality as well as the frequency/activation of immune populations hold significant potential for predicting response and elucidating the biology of anti-tumor immunity in stage 3 NSCLC treated with durvalumab. In this study, we sought to characterize clinical and immunologic predictors of durable response to therapy with a specific focus on TCR clonality and peripheral immune populations. Methods: Stage 3 NSCLC patients undergoing chemoradiation (CRT) and durvalumab were prospectively recruited and underwent baseline and serial blood collections. TCR repertoire analysis was performed on cfDNA using hybrid-capture TCR sequencing and TCR diversity estimated using Shannon’s entropy index. Viably preserved 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. Correlations between cell populations were examined using linear and cox regression. Results: 134 stage 3 NSCLC patients who received durvalumab had a median PFS was 15.4 months, with worse PFS in patients with PD-L1 1-49% (HR 2.4, p = 0.03) and PD-L1 < 1% (HR 2.6, p = 0.03). Smoking and EGFR/ALK mutations were not predictors of PFS. Immune profiling was performed in a pilot of 19 patients. Baseline TCR diversity did not associate with clinical factors or outcome. However, lack of clonal expansion after CRT indicated by a higher Shannon’s index was significantly associated with increased frequency of Tregs after durvalumab (p < 0.05). In turn, this elevation in Tregs was associated with significantly reduced PFS in EGFR/ALK wt patients (p = 0.03) and a trend towards reduced PFS in the overall cohort (HR 5.2, p = 0.1). Conclusions: Clonal expansion of T cells after CRT may influence the likelihood of an anti-tumor immune response following PD-L1 blockade in stage 3 NSCLC. Similarly, expansion of peripheral Treg populations is associated with increased likelihood of disease recurrence. Further characterization of TCR clonality, minimal residual disease and T cell subpopulations using serially collected blood is ongoing.
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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 | 0.001 |
| 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".