Abstract
The WHO’s classification of renal cell carcinoma (RCC) has identified loss of SMARCB1 as one of the driven mutations. Despite intensive postoperative interventions, the prognosis for SMARCB1-deficient medullary RCC remains poor, indicating insufficiency in current therapy. Herein, we reported the treatment outcomes of five patients with metastatic SMARCB1-deficient medullary RCC and molecular correlates. Four patients were treated with first-line immune checkpoint inhibitors (ICI) plus tyrosine kinase inhibitors (TKI) combination therapy with a median PFS (mPFS) of 12.3 months. Transcriptomic analysis revealed enrichment of immune-related pathways in SMARCB1-deficient medullary RCC compared to clear-cell and papillary RCC. Multiple immunofluorescence (mIF) revealed the association between the formation of mature tertiary lymphoid structures (TLSs) and the favorable response to ICI-based combination therapy. In conclusion, ICI-based combination therapy showed promising anti-tumor activity in SMARCB1-deficient medullary RCC patients. The presence of mature tertiary TLSs may partially elucidate the mechanism underlying treatment response.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
