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Exploiting Tertiary Lymphoid Structures to Stimulate Antitumor Immunity and Improve Immunotherapy Efficacy
Giulia Petroni1, Serena Pillozzi2, Lorenzo Antonuzzo1,3
1Department of Experimental and Clinical Medicine, University of Florence, Firenze, Italy.
Abstract:
Tumor-associated tertiary lymphoid structures (TLS) have been associated with favorable clinical outcomes and response to immune checkpoint inhibitors in many cancer types, including non-small cell lung cancer. Although the detailed cellular and molecular mechanisms underlying these clinical associations have not been fully elucidated, growing preclinical and clinical studies are helping to elucidate the mechanisms at the basis of TLS formation, composition, and regulation of immune responses. However, a major challenge remains how to exploit TLS to enhance naïve and treatment-mediated antitumor immune responses. Here, we discuss the current understanding of tumor-associated TLS, preclinical models that can be used to study them, and potential therapeutic interventions to boost TLS formation, with a particular focus on lung cancer research.
Insights
Tumor-associated tertiary lymphoid structures (TLS) in lung cancer correlate with better outcomes and immunotherapy response. Research is exploring how to enhance TLS to improve anti-tumor immunity and treatment effectiveness.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Tertiary lymphoid structures (TLS) in tumors are linked to improved patient prognosis and response to immune checkpoint inhibitors, particularly in non-small cell lung cancer.
- The precise mechanisms of TLS formation, composition, and immune regulation are still under investigation.
- A key challenge is leveraging TLS to amplify anti-tumor immune responses, both spontaneous and treatment-induced.
Purpose of the Study:
- To review the current understanding of tumor-associated TLS.
- To discuss preclinical models for studying TLS.
- To explore therapeutic strategies for enhancing TLS in cancer, with a focus on lung cancer.
Main Methods:
- Literature review and synthesis of current research on TLS in cancer.
- Discussion of established and emerging preclinical models for TLS investigation.
- Analysis of potential therapeutic interventions targeting TLS formation and function.
Main Results:
- TLS are associated with favorable clinical outcomes and immunotherapy response in various cancers, including lung cancer.
- Preclinical and clinical studies are progressively clarifying the roles of TLS in antitumor immunity.
- Significant challenges persist in therapeutically exploiting TLS to augment immune responses against tumors.
Conclusions:
- Understanding TLS biology is crucial for improving cancer immunotherapy.
- Targeting TLS represents a promising avenue for enhancing treatment efficacy in lung cancer.
- Further research into TLS modulation is warranted to optimize cancer treatment strategies.
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