To determine the overall tumor microenvironment (TME), characteristics, and transition mechanisms in primary central nervous system lymphoma (PCNSL), we performed spatial transcriptomics and matched the corresponding single-cell sequencing data of PCNSL patients. We found that tumor cells may achieve a “TME remodeling pattern” through an “immune pressure-sensing model”, in which they could choose to reshape the TME into a barrier environment or a cold environment according to the immune pressure. A key FKBP5⁺ tumor subgroup was found to be responsible for pushing tumors into the barrier environment, which provides a possible way to evaluate the stage of PCNSL. The specific mechanism of the TME remodeling pattern and the key molecules of the immune pressure-sensing model were identified through the spatial communication analysis. Finally, we discovered the spatial and temporal distributions and variation characteristics of immune checkpoint molecules and CAR-T target molecules in immunotherapy. These data clarified the TME remodeling pattern of PCNSL, provided a reference for its immunotherapy, and provided suggestions for the TME remodeling mechanism of other cancers.

为了确定原发性中枢神经系统淋巴瘤（PCNSL）的整体肿瘤微环境（TME）、特征和转化机制，我们进行了空间转录组学并匹配了PCNSL患者相应的单细胞测序数据。我们发现肿瘤细胞可能通过“免疫压力感知模型”实现“TME重塑模式”，根据免疫压力选择将TME重塑为屏障环境或冷环境。发现一个关键的FKBP5 ⁺肿瘤亚群负责将肿瘤推入屏障环境，这为评估 PCNSL 的阶段提供了一种可能的方法。通过空间通讯分析，确定了TME重塑模式的具体机制和免疫压力传感模型的关键分子。最后，我们发现了免疫治疗中免疫检查点分子和CAR-T靶分子的时空分布和变异特征。这些数据阐明了PCNSL的TME重塑模式，为其免疫治疗提供参考，并为其他癌症的TME重塑机制提供建议。