TFPI2 expression predicts resistance to immunotherapy plus tyrosine kinase inhibitor and informs first-line therapy selection in metastatic renal cell carcinoma.

Jiajun Wang, Lingzhi Du, Ying Wang, Hang Wang, Yanjun Zhu, Xianglai Xu

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Article in Cellular oncology (Dordrecht, Netherlands), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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6 authors.

Jiajun Wang *Department of Urology, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, 200032, China.

Lingzhi Du *Department of Urology, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, 200032, China.

Ying Wang *Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Hang WangDepartment of Urology, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, 200032, China. wang.hang@zs-hospital.sh.cn.

Yanjun ZhuDepartment of Urology, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, 200032, China. zhu.yanjun@zs-hospital.sh.cn.

Xianglai XuDepartment of Urology, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, 200032, China. xl.xu@hotmail.com.

Funding

Clinical Research Program of Shanghai Municipal Health Commission 20244Y0100National Natural Science Foundation of China 62273099National Natural Science Foundation of China 82200090National Natural Science Foundation of China 82472795Natural Science Foundation of Fujian Province 2023J05297Natural Science Foundation of Fujian Province 2024J08348Natural Science Foundation of Shanghai Municipality 24ZR1411000Science and Technology Commission of Shanghai Municipality 22Y11905300Zhongshan Hospital ZSLCYJ202338

6 · The paper itself

Abstract

purposeCombinations of anti-PD-1/PD-L1 immunotherapy (IO) and anti-VEGF tyrosine kinase inhibitor (TKI) are recommended as first-line therapy for metastatic renal cell carcinoma (RCC). We aimed to evaluate the predictive value of tissue factor pathway inhibitor 2 (TFPI2) for IO + TKI response.

methodsTFPI2 expression and its association with IO + TKI response and progression-free survival (PFS) were analyzed in the ZS-MRCC and JAVELIN Renal 101 cohorts. Tumor microenvironment analyses were conducted in ZS-HRRCC and TCGA-KIRC cohorts using RNA-sequencing, flow cytometry, immunohistochemistry, and immunofluorescence.

resultsTFPI2 expression was elevated in IO + TKI non-responders (p = 0.044) and predicted shorter PFS in ZS-MRCC (p = 0.026) and JAVELIN Renal 101 (p = 0.007) cohorts. Multivariate analysis confirmed TFPI2 as an independent prognostic factor (HR = 2.42; p = 0.030). High-TFPI2 tumors exhibited reduced Granzyme B

conclusionTFPI2 overexpression is associated with immune evasion and poor PFS in RCC patients treated with IO + TKI. The RF model may facilitate precision treatment selection between IO + TKI and TKI monotherapy.

Indexed as

Carcinoma, Renal CellDrug Resistance, NeoplasmGlycoproteinsImmunotherapyKidney NeoplasmsProtein Kinase InhibitorsAgedFemaleHumansMaleMiddle AgedNeoplasm MetastasisPrognosisTumor MicroenvironmentGlycoproteinsProtein Kinase Inhibitorstissue-factor-pathway inhibitor 2Immune evasionImmunotherapyRenal cell carcinomaTissue factor pathway inhibitor 2Tyrosine kinase inhibitor

Identifiers

PMID42171882

DOI10.1007/s13402-026-01224-3

PMCPMC13481657

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.