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Tertiary lymphoid structures potentially promote immune checkpoint inhibitor response in SMARCB1-deficient medullary renal cell carcinoma

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机构： [1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [2]Department of Pathology, West China Hospital, Sichuan University, Chengdu, China. [3]Department of Radiology, West China Hospital, Sichuan University, Chengdu, China

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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.© 2024. The Author(s).

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大类 | 1 区医学

小类 | 2 区肿瘤学

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第一作者机构： [1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

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