Soft-tissue sarcomas represent a heterogeneous group of cancer, with more than 50 histological subtypes^1,2. The clinical presentation of patients with different subtypes is often atypical, and responses to therapies such as immune checkpoint blockade vary widely^3,4. To explain this clinical variability, here we study gene expression profiles in 608 tumours across subtypes of soft-tissue sarcoma. We establish an immune-based classification on the basis of the composition of the tumour microenvironment and identify five distinct phenotypes: immune-low (A and B), immune-high (D and E), and highly vascularized (C) groups. In situ analysis of an independent validation cohort shows that class E was characterized by the presence of tertiary lymphoid structures that contain T cells and follicular dendritic cells and are particularly rich in B cells. B cells are the strongest prognostic factor even in the context of high or low CD8⁺ T cells and cytotoxic contents. The class-E group demonstrated improved survival and a high response rate to PD1 blockade with pembrolizumab in a phase 2 clinical trial. Together, this work confirms the immune subtypes in patients with soft-tissue sarcoma, and unravels the potential of B-cell-rich tertiary lymphoid structures to guide clinical decision-making and treatments, which could have broader applications in other diseases.

软组织肉瘤代表一组异质性癌症，具有超过 50 种组织学亚型^1,2。不同亚型患者的临床表现往往不典型，对免疫检查点阻断等疗法的反应差异很大^3,4. 为了解释这种临床变异性，我们在这里研究了 608 种软组织肉瘤亚型肿瘤的基因表达谱。我们根据肿瘤微环境的组成建立了基于免疫的分类，并确定了五种不同的表型：免疫低（A 和 B）、免疫高（D 和 E）和高度血管化（C）组。独立验证队列的原位分析表明，E 类的特征是存在包含 T 细胞和滤泡树突状细胞的三级淋巴结构，并且特别富含 B 细胞。^{即使在高或低 CD8 +}的情况下，B 细胞也是最强的预后因素T 细胞和细胞毒性内容物。在一项 2 期临床试验中，E 类组表现出改善的生存率和对使用 pembrolizumab 阻断 PD1 的高反应率。总之，这项工作证实了软组织肉瘤患者的免疫亚型，并揭示了富含 B 细胞的三级淋巴结构在指导临床决策和治疗方面的潜力，这可能在其他疾病中有更广泛的应用。