Immune Crosstalk Between Lymph Nodes and Breast Carcinomas, With a Focus on B Cells.
Immune Crosstalk Between Lymph Nodes and Breast Carcinomas, With a Focus on B Cells.
复制标题
DOI：
10.3389/fmolb.2021.673051
复制
发表时间：
2021
影响因子：
5
通讯作者：
Grigoriadis A
中科院分区：
文献类型：
--
作者：
Alberts E;Wall I;Calado DP;Grigoriadis A
淋巴结（LNs）是高度组织化的次级淋巴器官，反映了对感染、损伤或癌症存在的免疫反应。对乳腺癌患者肿瘤和淋巴结中免疫和基质特征的广泛分子和形态学分析揭示了指示疾病进展的新模式。在LNs中，存在称为生发中心（GCs）的动态结构，它作为B细胞发育和产生亲和力成熟记忆B和产生抗体的浆细胞的免疫中枢。作为全身免疫和局部免疫之间的桥梁，在无癌LNs中观察到GCs的频率，间质肿瘤浸润淋巴细胞的水平和癌症进展之间的关联。分散在整个肿瘤微环境（TME）或聚集成簇形成三级淋巴样结构（TLS），肿瘤浸润B细胞（til -B）的发生主要与实体癌的优越疾病轨迹有关。最近的TIL-B分析研究揭示了大量不同的TIL-B种群，它们的功能作用，以及它们是来自LN中的GC反应，还是来自TME中的局部GC样结构，这些都有待研究。然而，LNs作为转移前生态位的免疫原性、TME内的TIL-B群体和TLS的存在之间的相似之处将有助于解释局部和广泛的TIL-B反应及其对癌症进展到淋巴管的影响。因此，增强LN GC和/或TME中GC样结构的TIL-Bs反应的治疗方法是乳腺癌和其他癌症患者的新兴管理策略。
Lymph nodes (LNs) are highly organized secondary lymphoid organs, and reflective of immune responses to infection, injuries, or the presence of cancer. Extensive molecular and morphological analyses of immune and stromal features in tumors and LNs of breast cancer patients have revealed novel patterns indicative of disease progression. Within LNs, there are dynamic structures called germinal centers (GCs), that act as the immunological hubs for B cell development and generation of affinity matured memory B and antibody-producing plasma cells. Acting as a bridge between systemic and local immunity, associations are observed between the frequency of GCs within cancer-free LNs, the levels of stromal tumor infiltrating lymphocytes, and cancer progression. Scattered throughout the tumor microenvironment (TME) or aggregated in clusters forming tertiary lymphoid structures (TLS), the occurrence of tumor infiltrating B cells (TIL-Bs) has been linked mostly to superior disease trajectories in solid cancers. Recent TIL-Bs profiling studies have revealed a plethora of different TIL-B populations, their functional roles, and whether they are derived from GC reactions in the LN, and/or locally from GC-like structures within the TME remains to be investigated. However, parallels between the immunogenic nature of LNs as a pre-metastatic niche, TIL-B populations within the TME, and the presence of TLS will help to decipher local and widespread TIL-Bs responses and their influence on cancer progression to the lymphatics. Therapies that enhance TIL-Bs responses in the LN GC and/or in GC-like structures in the TME are thus emerging management strategies for breast and other cancer patients.