美国斯坦福大学Ansuman T. Satpathy和奥地利维也纳医科大学Juliane Winkler合作报道了乳腺癌转移过程中肺部免疫重构的时间进展。相关研究成果2024年5月30日在线发表于《癌细胞》杂志上。

据介绍，肿瘤转移需要对远端器官微环境进行系统性重塑，从而影响免疫细胞表型、群体结构和细胞间通讯。然而，人们对转移生态位中免疫表型动力学的理解仍然不完整。

研究人员在多瘤病毒中间T抗原（PyMT）和4T1转移性癌症模型中纵向测定了肺免疫转录谱，从原发性肿瘤发生，通过转移前生态位形成，到单细胞分辨率的转移生长的最后阶段。对这些数据的计算分析显示，外周来源和组织驻留的髓系细胞都制定了TLR-NFκB炎症程序，该程序与转移前的小生态位形成相关，并反映了原发肿瘤中CD14⁺“活化”的髓细胞。

此外，研究人员观察到原发性肿瘤和转移性小生境自然杀伤（NK）细胞在小鼠和人类患者样本中受到不同的调节，转移性小生态位的细胞毒性NK细胞比例升高。最后，研究人员确定了转移过程中IGF1和CCL6信号传导的细胞类型特异性动态调节，这代表了抗转移免疫疗法的候选途径。

附：英文原文

Title: The temporal progression of lung immune remodeling during breast cancer metastasis

Author: Christopher S. McGinnis, Zhuang Miao, Daphne Superville, Winnie Yao, Andrei Goga, Nathan E. Reticker-Flynn, Juliane Winkler, Ansuman T. Satpathy

Issue&Volume: 2024-05-30

Abstract: Tumor metastasis requires systemic remodeling of distant organ microenvironments thatimpacts immune cell phenotypes, population structure, and intercellular communication.However, our understanding of immune phenotypic dynamics in the metastatic niche remainsincomplete. Here, we longitudinally assayed lung immune transcriptional profiles inthe polyomavirus middle T antigen (PyMT) and 4T1 metastatic breast cancer models fromprimary tumorigenesis, through pre-metastatic niche formation, to the final stagesof metastatic outgrowth at single-cell resolution. Computational analyses of thesedata revealed a TLR-NFκB inflammatory program enacted by both peripherally derivedand tissue-resident myeloid cells that correlated with pre-metastatic niche formationand mirrored CD14+ “activated” myeloid cells in the primary tumor. Moreover, we observed that primarytumor and metastatic niche natural killer (NK) cells are differentially regulatedin mice and human patient samples, with the metastatic niche featuring elevated cytotoxicNK cell proportions. Finally, we identified cell-type-specific dynamic regulationof IGF1 and CCL6 signaling during metastatic progression that represents anti-metastaticimmunotherapy candidate pathways.

DOI: 10.1016/j.ccell.2024.05.004

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00167-3