Rajat Butola, Shinsheng Yuan, Grace S Shieh
Immune checkpoint inhibitors (ICIs) have improved outcomes for subsets of patients with metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma (mRCC), yet objective response rates remain low (∼15-25%), underscoring the need for tools that support patient stratification. We previously developed LogitDA, a logistic regression-based predictor incorporating feature selection and domain adaptation, which outperformed established immune-related signatures in predicting response to the PD-L1 inhibitor atezolizumab. Here, we present the ImmunoResponse Predictor, a web-based clinical decision-support framework that enables responsible application of LogitDA in real-world settings. The system integrates standardized transcriptomic preprocessing, interpretable individual-level predictions (including single-sample use), clinically motivated LogitDA score cutoffs that prioritize minimization of false negatives, and a cohort-level percentage of applicability with empirically derived thresholds designed to assess whether predictions can be reliably extrapolated to newly uploaded datasets. Importantly, applicability functions as a diagnostic safeguard against distributional shift rather than as a response predictor. We evaluated the framework across four independent cohorts, PCD4989g(mUC), PCD4989g(mRCC), the Moreno cohort, and the UNC-108 cohort. LogitDA achieved prediction accuracies of 0.69, 0.83, 0.86, and 0.53, with corresponding applicability estimates of 74%, 76%, 71%, and 48%, respectively, correctly identifying the UNC-108 cohort as one in which predictions warrant increased caution. Overall, the ImmunoResponse Predictor extends LogitDA into a practical, interpretable, and safeguarded tool for immunotherapy response prediction, supporting cautious clinical and translational use.