Advancements in tertiary lymphoid structures: Insights for cancer treatment

The field of cancer immunotherapy has seen revolutionary advancements with the introduction of immune checkpoint blockade therapies, notably those targeting PD-1/PD-L1, in the 21st century. Despite significant breakthroughs, the clinical efficacy of these therapies and engineered immune solutions like CAR-T cells is constrained to a subset of patients, primarily due to factors such as the immunosuppressive nature of the tumor microenvironment and tumor heterogeneity. This highlights a pressing need for innovative strategies that more effectively utilize the complex interplay of tumor-immune interactions.

Tertiary lymphoid structures (TLSs) are ectopic aggregates of lymphoid tissues comprising various immune cells, such as T cells, B cells, dendritic cells, and macrophages. Unlike secondary lymphoid organs, TLSs emerge de novo in non-lymphoid tissues, including tumors, as a result of chronic inflammation or immune responses. Recent studies indicate that TLSs boost local antigen presentation and lymphocyte activation, fostering potent anti-tumor immune reactions. Additionally, the presence of TLSs is associated with improved prognosis and increased immunotherapy responsiveness across various cancers. Investigating the development and functioning of TLSs within tumors offers a promising avenue for enhancing immunotherapeutic efficacy.

This Research Topic aims to collect pioneering research and thorough reviews on the biology and clinical significance of tertiary lymphoid structures in cancer. We aim to elucidate the regulatory mechanisms that underlie TLS development, their roles in local immune response modulation, and their potential as prognostic biomarkers or therapeutic targets. Through these insights, we strive to establish a foundation for developing TLS-centered interventions to bolster cancer immunotherapy. To deepen our understanding, we welcome articles addressing the following themes:

- The influence of TLSs on modulating the tumor's immune landscape.
- Molecular and cellular pathways driving TLS formation and maintenance in cancerous tissues.
- The role of TLSs in enhancing the efficacy of ICB and adoptive cell therapies.
- Discovery and validation of TLS-related biomarkers for prognostic and therapeutic predictions.
- Strategies to therapeutically induce or modify TLSs for improved anti-tumor immunity.
- Utilization of spatial transcriptomics, single-cell analyses, and computational modeling to explore TLS heterogeneity and function.

Through this collection, we aim to foster interdisciplinary insights and propel translational advancements in TLS-based cancer immunotherapy.

Appendix: We encourage the submission of Original Research, Reviews, and Opinion articles related to this theme.