Analysis of the immunological markers BTLA, TIM-3, and PD-L1 at the invasion front and tumor center in clear cell renal cell carcinoma.

Autor: Stühler V; Department of Urology, University Hospital Tuebingen, Eberhard-Karls-University Tuebingen, Tübingen, Germany., Alemi B; Department of Urology, University Hospital Tuebingen, Eberhard-Karls-University Tuebingen, Tübingen, Germany., Rausch S; Department of Urology, University Hospital Tuebingen, Eberhard-Karls-University Tuebingen, Tübingen, Germany., Stenzl A; Department of Urology, University Hospital Tuebingen, Eberhard-Karls-University Tuebingen, Tübingen, Germany., Schwab M; Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.; University of Tübingen, Tübingen, Germany.; Departments of Clinical Pharmacology, Pharmacy and Biochemistry, University of Tuebingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', Faculty of Medicine, University of Tübingen, Tübingen, Germany.; German Cancer Consortium (DKTK), Partner Site Tübingen, 72076, Tübingen, Germany., Schaeffeler E; Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.; University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', Faculty of Medicine, University of Tübingen, Tübingen, Germany., Bedke J; Department of Urology, University Hospital Tuebingen, Eberhard-Karls-University Tuebingen, Tübingen, Germany. bedke@live.com.; Department of Urology and Transplantation Surgery, Klinikum Stuttgart, Kriegsbergstraße 60, 70174, Stuttgart, Germany. bedke@live.com.
Jazyk: angličtina
Zdroj: World journal of urology [World J Urol] 2024 Jan 20; Vol. 42 (1), pp. 53. Date of Electronic Publication: 2024 Jan 20.
DOI: 10.1007/s00345-023-04721-4
Abstrakt: Purpose: Immune checkpoint inhibitors (ICI) are then backbone in the therapy of metastatic renal cell carcinoma (RCC). The aim of this analysis was to explore the different expression of the ICI PD-L1, BTLA, and TIM-3 at the different tumor locations of the invasion front and the tumor center.
Methods: Large-area sections of the tumor center and invasion front of 44 stage pT1-4 clear cell RCCs were examined immunohistochemically using antibodies against BTLA, TIM-3, and PD-L1 and subsequently correlated with clinicopathologic data.
Results: TIM-3 was most strongly expressed at the invasion front (mean ± SD: 84.1 ± 46.6, p = 0.094). BTLA expression was highest in normal tissue, with weak staining in the tumor center and at the invasion front [110.2 vs. 18.6 (p < 0.001) vs. 32.2 (p = 0.248)]. PD-L1 was weakly expressed at the tumor center (n = 5/44) and at the invasion front (n = 5/44). Correlation with clinicopathological parameters revealed significantly higher BTLA expression in ≥ T3 tumors compared to T1/2 tumors (tumor center p = 0.009; invasion front p = 0.005). BTLA-positive tumors at the tumor center correlated with worse CSS (median 48.46 vs. 68.91 months, HR 4.43, p = 0.061). PD-L1 expression was associated with worse CSS (median 1.66 vs. 4.5 years, HR 1.63, p = 0.652). For TIM-3, there were no significant associations with clinicopathological parameters and survival.
Conclusion: The present results show heterogeneous intratumoral and intertumoral expression of the investigated checkpoint receptors PD-L1, BTLA, and TIM-3. In the clinical practice tumor sampling should include different tumor locations, and multiple inhibition of different checkpoint receptors seems reasonable to increase the therapeutic success.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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