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Tertiary lymphoid structures in cancer: immune mechanisms and clinical implications
Siyu Wang1,2,3, Hua Wang1,2, Chenbei Li1,2
1Department of Orthopaedics The Second Xiangya Hospital of Central South University Changsha Hunan China.
Abstract:
Cancer is a major cause of death globally, and traditional treatments often have limited efficacy and adverse effects. Immunotherapy has shown promise in various malignancies but is less effective in tumors with low immunogenicity or immunosuppressive microenvironment, especially sarcomas. Tertiary lymphoid structures (TLSs) have been associated with a favorable response to immunotherapy and improved survival in cancer patients. However, the immunological mechanisms and clinical significance of TLS in malignant tumors are not fully understood. In this review, we elucidate the composition, neogenesis, and immune characteristics of TLS in tumors, as well as the inflammatory response in cancer development. An in-depth discussion of the unique immune characteristics of TLSs in lung cancer, breast cancer, melanoma, and soft tissue sarcomas will be presented. Additionally, the therapeutic implications of TLS, including its role as a marker of therapeutic response and prognosis, and strategies to promote TLS formation and maturation will be explored. Overall, we aim to provide a comprehensive understanding of the role of TLS in the tumor immune microenvironment and suggest potential interventions for cancer treatment.
Insights
Tertiary lymphoid structures (TLSs) are crucial in the tumor immune microenvironment, influencing immunotherapy response and patient survival. Understanding TLS composition and function can guide novel cancer treatment strategies.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Cancer remains a leading global cause of death, with traditional treatments facing limitations.
- Immunotherapy shows promise but is less effective in immunologically «cold» tumors, including sarcomas.
- Tertiary lymphoid structures (TLSs) correlate with better immunotherapy response and survival, yet their precise role is unclear.
Purpose of the Study:
- To review the composition, formation, and immune characteristics of TLS within the tumor immune microenvironment.
- To explore the specific immune roles of TLS in various cancers like lung, breast, melanoma, and soft tissue sarcomas.
- To discuss the therapeutic implications of TLS as prognostic and predictive biomarkers and strategies for their enhancement.
Main Methods:
- Comprehensive literature review on Tertiary Lymphoid Structures (TLS) in cancer.
- Analysis of immunological mechanisms and clinical significance of TLS.
- Discussion of TLS in specific cancer types and therapeutic strategies.
Main Results:
- TLS are key components of the tumor immune microenvironment, influencing treatment outcomes.
- TLS exhibit unique immune characteristics across different cancer types, impacting immunogenicity.
- TLS can serve as biomarkers for predicting therapeutic response and patient prognosis.
Conclusions:
- TLS play a significant role in modulating the tumor immune microenvironment and response to immunotherapy.
- Targeting TLS formation and maturation presents a promising avenue for improving cancer treatment efficacy.
- Further research into TLS biology is essential for developing effective cancer immunotherapies.
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