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Beyond TLS Presence: A Functional Framework Integrating Maturity, Location, and Immune Context
Jakub Kleinrok1, Kamil Rusztyn2,3, Marta Druszcz1
1Chair and Department of Clinical Pathomorphology, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland.
Cancers
|August 13, 2026
Summary
Tumor Loci (TLSs) are immune cell clusters in tumors. A new framework classifies TLSs into three functional states (TLS-A, TLS-B, TLS-C) based on maturity, location, and immune context for better clinical interpretation.
Area of Science:
- Immunology
- Oncology
- Pathology
Background:
- Tumor Loci (TLSs) are immune cell aggregates in non-lymphoid tissues, relevant in solid tumors.
- Current TLS assessment methods lack correlation with diverse clinical outcomes.
- TLSs are dynamic functional immune niches, not static findings.
Purpose of the Study:
- To propose a new framework for interpreting TLSs as functional immune niches.
- To classify TLSs into three functional states (TLS-A, TLS-B, TLS-C) based on biological, spatial, and clinical evidence.
- To provide a translational model for harmonizing TLS interpretation and biomarker development.
Main Methods:
- Synthesis of current biological, spatial, and clinical evidence on TLSs.
- Development of a conceptual framework classifying TLSs into functional states.
- Integration of histopathologic and molecular data for a proposed functional TLS score.
Main Results:
- Proposed classification of TLSs into three functional states: TLS-A (mature effector), TLS-B (intermediate), and TLS-C (suppressive).
- Framework integrates structural maturity, spatial localization, and immune context.
- Framework aims to refine understanding of TLSs in tumor microenvironment archetypes.
Conclusions:
- The proposed framework offers a pragmatic model for interpreting TLSs in solid tumors.
- This approach facilitates biomarker development and standardized pathology reporting.
- Further prospective, tumor-specific validation is required before clinical implementation.
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