转移性透明细胞肾细胞癌具有异质肿瘤微环境（TME）。在转移性病灶中，胰腺转移很少见，治疗方法也存在争议。在这里，单细胞 RNA-seq 纳入了大量的原发性和转移性病变样本，以破译不同的转移性 TME。本研究解码了胰腺转移的缺氧和炎症TME，并观察了PAX8-myc信号的激活和代谢重编程。对包括内皮细胞、成纤维细胞和 T 细胞在内的活性成分进行了分析。同时，我们还评估了胰腺转移患者抗血管生成治疗的效果。这项工作还讨论了胰腺向性、基因组不稳定性和免疫治疗反应的潜在机制。总而言之，我们的研究结果为 TME 转移的异质性提供了线索，并为肾细胞癌患者胰腺转移的治疗提供了证据。版权所有 © 2024。由 Elsevier B.V. 出版。

Metastatic clear cell renal cell carcinoma has heterogenous tumor microenvironment (TME). Among the metastatic lesions, pancreas metastasis is rare and controversy in treatment approaches. Here, extensive primary and metastatic lesion samples were included by single-cell RNA-seq to decipher the distinct metastasis TME. The hypoxic and inflammatory TME of pancreas metastasis was decoded in this study, and the activation of PAX8-myc signaling, and metabolic reprogramming were observed. The active components including endothelial cells, fibroblasts and T cells were profiled. Meanwhile, we also evaluated the effect of anti-angiogenesis treatment in the pancreas metastasis patient. The potential mechanisms of pancreatic tropism, instability of genome, and the response of immunotherapy were also discussed in this work. Taken together, our findings suggest a clue to the heterogeneity in metastasis TME and provide evidence for the treatment of pancreas metastasis in renal cell carcinoma patients.Copyright © 2024. Published by Elsevier B.V.