Background: This prospective pilot study explored the potential of the innate immune system’s response to cancer-related immuno-stimulants as a predictive biomarker for Immune Checkpoint Inhibitor (ICI) effectiveness, using pembrolizumab-treated metastatic urothelial tract cancer (mUTC) patients as the study population. Methods: We included ten mUTC patients and assessed their innate immune responses before the first and second pembrolizumab cycles with the TruCulture® immunoassay. We also executed survival analysis and compared cytokine release. Results: R848-induced IFNα and HKCA-induced IL-10 values decreased in patients with disease progression (n = 7), while these values increased in non-progressing patients (n = 3), denoting a significant difference (p = 0.00192 and p = 0.00343, respectively). Further, an increased R848-induced IFNα response correlated with extended survival (log-rank p-value of 0.048). Conclusion: Our small study identified distinct immune response patterns following pembrolizumab’s first cycle in mUTC patients, hypothesizing the potential of an increased R848-induced IFNα response for improved survival outcomes. Further confirmatory studies are in progress.
