Immunological profile of the tumor immune microenvironment of upper tract urothelial carcinoma predicts recurrence patterns

The association between the tumor immune microenvironment (TiME) in upper tract urothelial carcinoma (UTUC) and its prognosis remains unclear. We investigated the relationship between TiME and UTUC recurrence patterns.

We evaluated 90 patients who underwent nephroureterectomy for UTUC and divided them into nonrecurrence, distant metastasis, and intravesical recurrence-only groups. We assessed the association of the TiME with clinicopathological factors using surgical tissues and the prognosis of the three groups via multiplex fluorescence immunohistochemistry.

The median age was 71 years (44-89), and 58 (64%) were male. Intratumoral CD4⁺ T cell density was significantly higher in the nonrecurrence group (p = 0.0004) than the other groups, whereas intra- and peritumoral regulatory T cell (Treg; CD3⁺CD4⁺FoxP3⁺ cell) density was higher in the distant metastases group than the intravesical recurrence-only group (p = 0.0025). In the multivariate analysis, pathological T stage and CD4⁺ T cells, and pathological T stage and Treg were independent predictors of recurrence-free survival (p = 0.045, p = 0.017) and metastatic-free survival (p = 0.027, p = 0.011), respectively.

Our study demonstrated that CD4⁺ T cells and Tregs in the TiME of patients with UTUC were independent predictors of high-risk recurrence together with high pathological stage. The analysis of TiME in surgical specimens may provide an objective indicator of the efficacy of adjuvant therapy in UTUC.