Purpose: The aim of this study was to determine whether CD8⁺ T lymphocyte and its checkpoint-associated module programmed cell death protein 1 (PD-1)/main ligand of PD-1 (PD-L1) pathway impact overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs). Materials and methods: A total of 231 mRCC patients, from 2007 to 2017, treated with sunitinib or sorafenib in Zhongshan Hospital, Fudan University were included in the study analyses. CD8, PD-1, and PD-L1 was assessed by immunohistochemistry on continuous paraffin-embedded slides. Kaplan–Meier method and COX regression model were applied in the survival analyses. Results: Baseline characteristics were comparable between the training (n=118) and validation (n=113) sets. Patients with high CD8⁺ T lymphocytes infiltration and low PD-1 expression had longer survival in both sets (P=0.0106 and P=0.0047 in training set, P=0.0291 and P=0.0011 in validation set, respectively). However, survival stratified by PD-L1 was only insignificant or marginally significant. Multivariable analyses verified that CD8⁺ T lymphocytes, together with PD-1, but not tumor infiltrating mononuclear cells or tumor cells PD-L1, were independent prognostic factors (training set [HR 3.202, 95% CI 1.433–7.153, P=0.011] and validation set [HR 4.012, 95% CI 2.354–6.838, P<0.001]). Subsequent analysis revealed that the PD-1 high/CD8 low group had shorter survival (16 months) than PD-1 low/CD8 high group (51 months, P<0.0001). Combining the International Metastatic Renal Cancer Database Consortium system with the PD-1/CD8 model exhibited much better accuracy for the prediction of OS. Conclusion: Our findings suggest that abundant CD8⁺ T cells are significantly associated with longer OS in mRCC patients treated with TKIs. The most influential checkpoint-associated molecule, PD-1, assisted CD8⁺ T cell-stratified patients and could be used as a better predictive and prognostic factor for the mRCC patients.

Introduction: Vimentin, a classical marker of epithelial–mesenchymal transition, reflects the invasiveness of cancer cells. Its role in the genesis and progression of tumor has been reported in various cancers, including renal cell carcinoma. However, the impact of vimentin on tumor microenvironment, particularly its implication with tumor-infiltrating immune cells, is unknown. Methods: We conducted this study in 231 patients with metastatic renal cell carcinoma (mRCC) to determine the potential relationship between vimentin and immune status. Using immunohistochemical staining, expression of vimentin, CD8, FOXP3, programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1) were evaluated in resected tumor tissue. Kaplan–Meier analysis and Cox regression models were used for survival analysis. Chi-square test, Fisher exact test, and Mann–Whitney U-test were used for comparison between vimentin high and low groups. Results: High expression of vimentin, stroma PD-L1, and PD-1 indicated poor overall survival, whereas low regulatory T cell or high CD8+ T cell infiltration indicated long overall survival. Stroma PD-L1 (P = 0.030), vimentin (P = 0.026) expression, and CD8⁺ T cell infiltration (P < 0.001) were independent prognostic factors in mRCC. High vimentin expression was accompanied by high PD-1, PD-L1 expression, and increased regulatory T cell infiltration (all P < 0.001), indicating immunosuppression in the tumor microenvironment. Conclusions: We revealed that vimentin expression was associated with immunosuppression in mRCC, and the immune-suppressive status might be possibly posed by PD-1/PD-L1. Patients with high vimentin expression may acquire potential benefit from the recently approved PD-1/PD-L1 inhibitors. However, further clinical trials are needed to validate our findings.

Aim: Renal cell carcinoma (RCC), the most frequent type of primary renal malignancies, has a high mortality rate. Serine/threonine kinase 39 (STK39) is associated with various human diseases, including cancers. The current study aimed to investigate the functions of STK39 in RCC. Materials and methods: STK39 expression levels in RCC and paired normal renal tissue samples were detected by real-time polymerase chain reaction and Western blotting analyses. The biological functions of STK39 were explored in two RCC cell lines with STK39 silence. Results: STK39 expression was significantly increased in RCC tissues than in normal renal tissues. Suppression of STK39 expression in ACHN and 786-0 cells significantly suppressed cell proliferation and induced cell apoptosis. Consistently, the expression of PCNA and Bcl-2 was remarkably increased, while the expression of Bax was significantly in STK39 knockdown cells compared to control cells. Furthermore, gene set enrichment analysis identified STK39 as an important regulator of p53 and p38 signaling pathways. STK39 knockdown increased p53 expression and inhibited p38 phosphorylation. Moreover, ectopic expression of STK39 in ACHN cells resulted in a reduced p53 expression and increased c-Myc and p-p38 expression. Such effects were suppressed by p38 inhibitor (SB203580). Conclusion: STK39 may exert its oncogenic function in RCC through p38 signaling. Our data suggest that STK39 may represent a potential therapeutic target against RCC.

The objective of this study is to investigate the optimal therapeutic protocol for BSSRCC. A total of 32 BSSRCC patients, including 28 males and 4 females, were enrolled the study from January 2004 to May 2016. The diagnoses were defined by the measurements of CT, ultrasound, and MRI. Patients with hereditary syndrome were excluded. The management of surgical manner, operation staging, and sequence were scheduled in accordance with the tumor’s location and size (based on Zhongshan score, ZS score), as well as the performance status of the patients. Among them, 8 cases were conducted with bilateral surgical procedure simultaneously and 24 cases were implemented with staged operations. NSS on the one side with contralateral RN, and NSS on both sides were performed in 17 and 15 patients separately. Thirty cases were conducted 56 operations in total. The average operation time was 260 ± 52 min in simultaneous operations and 162 ± 40 min in staged operations. The length of hospital stay in average was 11.5 ± 1.8 and 7.5 ± 1.4 days, respectively. Twenty-eight cases were followed up by 6–138 months. The level of creatinine was elevated in 5 cases without hemodialysis conducted. The location and size of the carcinomas, and the performance status of patients should be considered in determination of an appropriate surgical approach. Both renal function preservation and tumor eradication were similarly critical, whereas the latter is of more importance. ZS score may be helpful in the dilemma. Longer follow-up period and more patient enrolment are required.

Background: Disitamab vedotin (DV, RC48-ADC) has shown promising efficacy and manageable safety as monotherapy or combined with immune checkpoint inhibitors (ICIs) in metastatic urothelial carcinoma (mUC) patients progressing after systemic chemotherapy. This study evaluates the efficacy and safety of RC48-ADC plus ICIs in metastatic upper tract urothelial carcinoma (mUTUC) in a real-world setting. Methods: This retrospective, multicenter study included 198 mUTUC patients treated with RC48-ADC plus ICI at 23 clinical centers between June 2021 and December 2023. Data were analyzed from July to September 2024. Primary endpoint: objective response rate (ORR). Secondary endpoints: progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to objective response, and treatment-related adverse events (TRAEs). Result: Among the patients, 122 (61.6%) received combination therapy as first-line treatment, while 76 (38.4%) as second-line or beyond. ORR was 58.6% (95% CI: 51.4–65.5), with a median PFS of 13.0 months; median OS was not reached. Subgroup analyses showed consistent ORR across all subgroups. Adverse events (AEs) occurred in 79.8% of patients, with grade 3–4 AEs in 19.7%. Common AEs included neuropathy (40.4%), fatigue (26.8%), alopecia (25.3%), and rash (21.7%). The main limitations of this study include its retrospective design and the population of the study only include patients from China, leading to potential selection bias. Conclusions: RC48-ADC combined with ICIs demonstrated robust antitumor activity and a favorable safety profile in real-world mUTUC, particularly in selected patient groups. Further studies are needed to explore its potential in this high-risk population.