1. Tertiary lymphoid structures potentially promote immune checkpoint inhibitor response in SMARCB1-deficient medullary renal cell carcinoma
- Author
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Yanfeng Tang, Junru Chen, Mengxin Zhang, Xu Hu, Jingjing Guo, Yaowen Zhang, Yuntian Chen, Haoyang Liu, Junjie Zhao, Ni Chen, Guangxi Sun, and Hao Zeng
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
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
- 2024
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