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Updated: Feb 13, 2026

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Tumor-Resident Streptococcus pneumoniae Promotes Malignant Progression and Pazopanib Resistance in Clear Cell Renal

Jinpeng Wang1,2, Yunfeng Nan1,2, Qing Liu2,3

  • 1Department of Urology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Cancer Research
|February 11, 2026
PubMed

Insights

Streptococcus pneumoniae in tumors drives pazopanib resistance in clear cell renal cell carcinoma (ccRCC) by altering lipid metabolism. This bacterium may serve as a biomarker for predicting patient response to this tyrosine kinase inhibitor.

Area of Science:

  • Oncology
  • Microbiology
  • Metabolic Research

Background:

  • Drug resistance to tyrosine kinase inhibitors (TKIs) limits survival in clear cell renal cell carcinoma (ccRCC).
  • Intratumoral bacteria have been implicated in cancer progression and treatment response.

Purpose of the Study:

  • To investigate the role of intratumoral microbiota in pazopanib resistance in ccRCC.
  • To identify specific bacteria associated with treatment resistance and elucidate their mechanisms of action.

Main Methods:

  • Microbiome screening of ccRCC patient samples treated with pazopanib.
  • Analysis of lipid metabolism reprogramming and molecular pathways in ccRCC cells.
  • Investigation of bacterial interactions with host cell proteins and metabolites.

Main Results:

  • Streptococcus pneumoniae (S. pneumoniae) was identified as the dominant intratumoral bacterium in pazopanib-resistant ccRCC.
  • S. pneumoniae depletes manganese (Mn2+), suppresses S-nitrosylation of TRIM28, and promotes lipid deposition via SP1/SLC27A1 axis.
  • This reprogramming facilitates malignant progression and pazopanib resistance.

Conclusions:

  • Tumor-resident S. pneumoniae contributes to pazopanib resistance in ccRCC by manipulating host lipid metabolism.
  • S. pneumoniae represents a potential predictive biomarker for pazopanib response in ccRCC patients.

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