Morphological alterations in cancer-free and cancer-involved axillary lymph nodes hold predictive prognostic information for breast cancer patients. 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. 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. 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. 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. 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. 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. 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. Lymph nodes (LNs) are highly organized secondary lymphoid organs, and reflective of immune responses to infection, injuries, or the presence of cancer. 4Immunity and Cancer Laboratory, The Francis Crick Institute, London, United Kingdom.3Faculty of Life Sciences and Medicine, School of Cancer & Pharmaceutical Sciences, King’s College London, London, United Kingdom.2Breast Cancer Now Unit, School of Cancer and Pharmaceutical Sciences, King’s College London, London, United Kingdom.1Faculty of Life Sciences and Medicine, Cancer Bioinformatics, School of Cancer & Pharmaceutical Sciences, King’s College London, London, United Kingdom.Elena Alberts 1,2,3, Isobelle Wall 1,2,3, Dinis Pedro Calado 4 and Anita Grigoriadis 1,2,3*
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