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A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
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Tertiary lymphoid structures potentially promote immune checkpoint inhibitor response in SMARCB1-deficient medullary

Yanfeng Tang1, Junru Chen1, Mengxin Zhang2

  • 1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

NPJ Precision Oncology
|November 14, 2024
PubMed

Insights

Immune checkpoint inhibitors plus tyrosine kinase inhibitors show promise for treating advanced SMARCB1-deficient medullary renal cell carcinoma (RCC). Mature tertiary lymphoid structures correlate with better responses to this combination therapy.

Area of Science:

  • Oncology
  • Genitourinary Pathology
  • Cancer Immunology

Background:

  • Loss of SMARCB1 is a key mutation in renal cell carcinoma (RCC) per WHO classification.
  • SMARCB1-deficient medullary RCC has a poor prognosis despite current treatments.
  • Novel therapeutic strategies are needed for this aggressive subtype.

Purpose of the Study:

  • To evaluate treatment outcomes in patients with metastatic SMARCB1-deficient medullary RCC.
  • To explore molecular correlates of treatment response.
  • To assess the efficacy of immune checkpoint inhibitors (ICI) plus tyrosine kinase inhibitors (TKI) combination therapy.

Main Methods:

  • Retrospective analysis of five metastatic SMARCB1-deficient medullary RCC patients.
  • Treatment with first-line ICI plus TKI combination therapy.
  • Transcriptomic analysis and multiple immunofluorescence (mIF) for molecular correlates.

Main Results:

  • Four patients received ICI + TKI combination therapy, achieving a median progression-free survival (mPFS) of 12.3 months.
  • Transcriptomics showed enriched immune-related pathways in SMARCB1-deficient medullary RCC.
  • Mature tertiary lymphoid structures (TLSs) observed via mIF correlated with favorable responses to ICI-based therapy.

Conclusions:

  • ICI-based combination therapy demonstrates promising anti-tumor activity in SMARCB1-deficient medullary RCC.
  • Mature TLSs may be a biomarker for predicting response to ICI-based combination therapy.
  • Further research is warranted to optimize treatment for this RCC subtype.

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