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A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Tertiary lymphoid structures in renal cell carcinoma: from heterogeneity dissection to translational precision
Zhexian Li1,2, Sensen Ruan1, Yang Yu1
1Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Abstract:
Renal cell carcinoma (RCC), characterized by its distinctive hypoxic and immunosuppressive tumor microenvironment (TME), demonstrates suboptimal responses to current immunotherapeutic interventions. Tertiary lymphoid structures (TLS), defined as ectopically organized immune cell aggregates that develop in non-lymphoid tissues, function as "plastic immune organs" and exhibit considerable promise as both prognostic indicators and therapeutic targets. Notably, TLS in RCC manifest significant heterogeneity, with specific subsets associated with favorable clinical outcomes while others correlate with adverse prognosis. This review systematically examines the cellular composition, formation, classification criteria, and evaluation methods of TLS in RCC, with particular emphasis on the relationship between TLS heterogeneity and differential prognostic implications. We further explore potential regulatory mechanisms underlying these divergent clinical outcomes and provide a comprehensive synthesis of current TLS-targeted therapeutic strategies, including recent clinical advancements. Finally, we delineate the prevailing challenges in TLS research and propose future directions. This work provides a theoretical foundation and research framework for future patient outcome-oriented prospective studies and clinical trials, while also offering insights for the development of TLS-related precision immunotherapy strategies.
Insights
Tertiary lymphoid structures (TLS) in renal cell carcinoma (RCC) show varied prognostic value due to tumor microenvironment (TME) heterogeneity. Understanding TLS is key for developing targeted immunotherapies and improving patient outcomes.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Renal cell carcinoma (RCC) features a hypoxic and immunosuppressive tumor microenvironment (TME), limiting immunotherapy effectiveness.
- Tertiary lymphoid structures (TLS) are immune cell aggregates in non-lymphoid tissues, acting as "plastic immune organs" with prognostic and therapeutic potential in RCC.
- TLS exhibit significant heterogeneity in RCC, with distinct subsets correlating with either favorable or adverse clinical outcomes.
Purpose of the Study:
- To systematically review the cellular composition, formation, classification, and evaluation of TLS in RCC.
- To emphasize the relationship between TLS heterogeneity and differential prognostic implications in RCC.
- To explore regulatory mechanisms of divergent clinical outcomes and synthesize current TLS-targeted therapeutic strategies.
Main Methods:
- Systematic literature review and synthesis of existing research on TLS in RCC.
- Analysis of cellular composition, formation pathways, and classification criteria of TLS.
- Evaluation of prognostic significance and therapeutic targeting of TLS in RCC.
Main Results:
- TLS heterogeneity in RCC is linked to varied clinical outcomes, impacting patient prognosis.
- Specific TLS subsets are associated with favorable prognoses, while others indicate adverse outcomes.
- Current TLS-targeted therapies show promise, with ongoing clinical advancements.
Conclusions:
- TLS heterogeneity is a critical factor in RCC prognosis and response to immunotherapy.
- Further research into TLS regulatory mechanisms and targeted strategies is essential for precision immunotherapy.
- This review provides a framework for future studies and clinical trials focused on TLS in RCC.
