# Grow immune command posts inside tumours

Source: https://onco.cc/ideas/idea-bio2-tertiary-lymphoid-induction/  
OnCo record `idea-bio2-tertiary-lymphoid-induction` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Tumours that contain small immune structures resembling lymph nodes respond far better to immunotherapy. Inducing those structures on purpose could make cold tumours responsive.

## Summary

Tertiary lymphoid structures and B-cell aggregates are among the strongest predictors of checkpoint response in sarcoma, melanoma and renal cancer. Their formation depends on LIGHT, lymphotoxin, CXCL13 and stromal organiser cells, and vascular-targeted LIGHT fusions induced them in mouse tumours. No clinical programme currently has tertiary lymphoid structure induction as its declared primary mechanism.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: An induction regimen based on LIGHT or CXCL13 delivery generates measurable tertiary lymphoid structures in serial biopsies of cold tumours, and their appearance is accompanied by intratumoural clonal T-cell expansion.
- Rationale: The association between these structures and response is unusually strong and reproducible across tumour types and datasets, and murine induction is achievable. Sarcoma trials already stratify by a B-cell-rich immune class, providing a ready-made target population.
- Proposed test: Phase 1 with mandatory serial biopsies in immune-class-defined sarcoma or renal cancer, primary endpoint the histological appearance of new lymphoid structures, secondary endpoint T-cell clonal expansion.
- Maturity: preclinical-evidence
- Actor: research

## Sources

- Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019): https://doi.org/10.1001/jamanetworkopen.2019.2535

## Connected records

- cancers: [Melanoma](https://onco.cc/cancers/melanoma/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/)
- technologies: [Cytokines & engineered cytokines](https://onco.cc/technologies/cytokine-therapy/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Single-cell & spatial profiling](https://onco.cc/technologies/single-cell-spatial/)
- terms: [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [Tumour-infiltrating lymphocytes (TILs)](https://onco.cc/terms/tils/)
- people: [Jean-Yves Blay](https://onco.cc/people/jean-yves-blay/)
- bottlenecks: [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/)
- key papers: [Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs](https://onco.cc/key-papers/paper-haslam-jama-netw-open/)

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