Tertiary lymphoid structures (TLSs) develop in non-lymphatic tissue in chronic inflammation and cancer. TLS can mature to lymph node (LN) like structures with germinal centers and associated vasculature. TLS neogenesis in cancer is highly varied and tissue dependent. The role of TLS in adaptive antitumor immunity is of great interest. However, data also show that TLS can play a role in cancer metastasis. The importance of lymphatics in cancer distant metastasis is clear yet the precise detail of how various immunosurveillance mechanisms interplay within TLS and/or draining LN is still under investigation. As part of the tumor lymphatics, TLS vasculature can provide alternative routes for the establishment of the pre-metastatic niche and cancer dissemination. The nature of the cytokine and chemokine signature at the heart of TLS induction can be key in determining the success of antitumor immunity or in promoting cancer invasiveness. Understanding the biochemical and biomechanical factors underlying TLS formation and the resulting impact on the primary tumor will be key in deciphering cancer metastasis and in the development of the next generation of cancer immunotherapeutics.
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http://dx.doi.org/10.3389/fmolb.2021.661516 | DOI Listing |
Curr Vasc Pharmacol
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Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
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Department of Neurosurgery, The First Affiliated Hospital, Guangxi Medical University, Nanning, China.
The tertiary lymphoid structure (TLS) is recognized as a potential prognosis factor for breast cancer and is strongly associated with response to immunotherapy. Inducing TLS neogenesis can enhance the immunogenicity of tumors and improve the efficacy of immunotherapy. However, our understanding of TLS associated region at the single-cell level remains limited.
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Interdisciplinary Oncology, University of British Columbia, Vancouver, Canada; Molecular and Advanced Pathology Core, University of British Columbia, Vancouver, Canada; Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada. Electronic address:
Immunotherapy has emerged as a new treatment modality in some soft tissue sarcomas, particularly for tumors associated with tertiary lymphoid structures (TLS). These structures are functional lymphoid aggregates, and their presence is indicative of an active anticancer immune response in the tumor microenvironment. The assessment of TLS as a predictive biomarker at scale on patient specimens remains challenging.
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