Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy. Hypoxia-inducible factors, HIF-1α and HIF-2α, are expressed in the majority of ccRCC. Targeting immune checkpoints with the blockade of PD-1 and its ligand PD-L1 reorganizes T-cell activity in tumor microenvironment and provides important antitumor responses. PD-L1 upregulation has been found to be hypoxia-inducible factor (HIF) dependent. Our aim is to demonstrate the association between PD-L1 and HIF expression and to reveal the role of PD-L1 in prognosis and its association with tumor microenvironment. Surgical specimens from 145 patients diagnosed with ccRCC, who had undergone radical or partial nephrectomy, were retrospectively analyzed. Immunohistochemistry on tissue microarrays (TMA) was performed to demonstrate expressions of PD-L1, HIF-1α, and HIF-2α in tumor cells and PD-1, CD4, and CD8 in lymphocytes to assess lymphocyte density in tumor microenvironment. PD-L1 tumor cell expression was detected in 20/125 (13.8%) cases, which correlated with higher levels of PD-1, CD4, CD8 and HIF-2α expression. Low or high expression of HIF-1α was similar in PD-L1-positive cases. When PD-L1-positive cases were compared with negative ones, there was no significant difference in terms of prognostic factors. However, the number of WHO/ISUP grade 3–4 tumors was significantly higher in PD-L1-positive cases than in negative ones. PD-L1 tumor cell expression is strongly associated with increased HIF-2α expression and presence of dense lymphocytic infiltration in ccRCCs. Our findings confirm that PD-L1 positivity is associated with high ISUP nucleolar grade. The association between PD-L1, HIF, and lymphocyte density in tumor microenvironment must be clarified and especially taken into account in combination treatment.

Background/Objectives: The optimal adjuvant chemotherapy regimen remains uncertain for some patients with hormone receptor (HR)-positive/HER2-negative early breast cancer, particularly regarding the incremental benefit of anthracyclines. We compared real-world outcomes with docetaxel-plus-cyclophosphamide (TC) and anthracycline–taxane chemotherapy. Methods: This retrospective single-center cohort included patients with stage I–III HR-positive/HER2-negative breast cancer who underwent surgery and received adjuvant TC or anthracycline–taxane chemotherapy between 2019 and 2025. Patients receiving neoadjuvant systemic therapy were excluded. Disease-free survival (DFS) was the primary outcome and overall survival (OS) the secondary outcome. Propensity score overlap weighting adjusted for measured baseline differences was used; the absolute difference in weighted 3-year DFS was the primary adjusted measure. Results: Among 361 patients, 201 received TC and 160 anthracycline–taxane chemotherapy. The anthracycline–taxane group had higher baseline clinicopathologic risk. Median follow-up was 39.0 months. Twelve DFS events occurred (TC, n = 3; anthracycline–taxane, n = 9). Unadjusted 3-year DFS was 99.0% versus 96.6% (p = 0.096), and 3-year OS was 99.4% versus 99.1% (p = 0.725). The overlap-weighted analysis included 346 patients and achieved adequate covariate balance. Weighted 3-year DFS was 99.2% with TC and 96.5% with anthracycline–taxane chemotherapy, an absolute difference of 2.68 percentage points (95% CI, −1.81 to 10.03). Sensitivity analysis yielded similar results (2.70 percentage points; 95% CI, −1.76 to 9.87). Conclusions: No statistically significant difference in 3-year DFS was demonstrated after adjustment. Limited events and relatively short follow-up preclude conclusions regarding equivalence or noninferiority. These findings support individualized adjuvant chemotherapy selection and warrant confirmation in larger cohorts with longer follow-up.