Immune biomarkers and treatment response
Fixed, low-dimensional immune-expression scores in public checkpoint-inhibitor cohorts: whether they change on treatment, whether they add information about response, and how far predictions transport to another cohort.
What changes in paired tumor immune-expression measurements during nivolumab?
Fixed immune scores in 43 public RNA pairs, with paired change, normalization sensitivity and patient-separated response-association diagnostics.
- In 43 public pre/on-nivolumab RNA pairs, a fixed cytolytic score rose in 33 of 43 participants (median +0.346, 95% interval +0.154 to +1.108), stable across FPKM and CPM (Spearman 0.996).
- Adding the change to baseline expression raised held-out response AUC from 0.599 to 0.673, but the interval (−0.084 to +0.269) included no improvement, with only nine responders.
- An observed on-treatment change is pharmacodynamic evidence, not a qualified predictive biomarker; biopsy dates, selection into a second biopsy and a validation cohort are needed next.
Do two immune-biology scores improve response prediction across urothelial cancer cohorts?
Fixed Teff and stromal features evaluated across public urothelial cancer cohorts, with discrimination, calibration, missingness and transport limits.
- Adding fixed T-effector and stromal RNA scores to a minimal clinical model raised cross-validated response AUC from 0.509 to 0.645 in the development cohort (298 patients, 68 responders).
- In the external-source cohort (72 patients, 11 responders), the fixed model reached AUC 0.554 (95% interval 0.367–0.725) and probability calibration was poor.
- The two scores support a biological hypothesis worth further study, not a clinically useful biomarker, an individual response probability or a prediction of who benefits from checkpoint inhibition.