Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

Area of Science:

• Oncology
• Immunology
• Pathology

Background:

• The tumor microenvironment is a complex, patient-specific ecosystem.
• Current therapies targeting tumor cells, angiogenesis, or immune cells offer limited long-term benefits and frequent relapses.
• Immune checkpoint inhibitors (ICIs) show promise but not all patients respond, even with
• hot
• tumors.

Purpose of the Study:

• To review the role of tertiary lymphoid structures (TLS) in cancer.
• To explore the relationship between TLS, tumor molecular characteristics, oncogenic viruses, and targeted therapies.
• To discuss TLS in non-tumor inflammatory diseases and novel research approaches.

Main Methods:

• Review of existing literature on tertiary lymphoid structures (TLS) in various tumors.
• Analysis of the association between TLS presence, tumor characteristics, and patient outcomes.
• Discussion of pre-clinical models, spheroids, organoids, and AI for TLS research.

Main Results:

• Tertiary lymphoid structures (TLS), ectopic lymphoid organs in tumors, are associated with improved long-term survival in most solid tumors.
• TLS presence predicts response to immune checkpoint inhibitors (ICIs).
• TLS share biological characteristics with those found in non-tumor inflammatory diseases.

Conclusions:

• Understanding TLS biology is key to improving prognostic prediction and treatment selection in cancer patients.
• Targeting TLS holds potential for next-generation cancer immunotherapy.
• Further research into TLS function and neogenesis is essential for advancing cancer care.