{"entity":{"id":"idea-bio2-tertiary-lymphoid-induction","kind":"idea","name":"Grow immune command posts inside tumours","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"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)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["sarcoma","rcc","melanoma"],"sections":[],"technologies":["single-cell-spatial","checkpoint-inhibitor","cytokine-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tils","cold-vs-hot"],"trials":[],"people":["jean-yves-blay"],"bottlenecks":["b-tme-immunosuppression","b-immunotherapy-response"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"medium","horizonYears":8},"route":"/ideas/idea-bio2-tertiary-lymphoid-induction/","neighbours":{"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}],"technology":[{"id":"cytokine-therapy","kind":"technology","name":"Cytokines & engineered cytokines","route":"/technologies/cytokine-therapy/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"}],"term":[{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"tils","kind":"term","name":"Tumour-infiltrating lymphocytes (TILs)","route":"/terms/tils/"}],"person":[{"id":"jean-yves-blay","kind":"person","name":"Jean-Yves Blay","route":"/people/jean-yves-blay/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"paper":[{"id":"paper-haslam-jama-netw-open","kind":"paper","name":"Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs","route":"/key-papers/paper-haslam-jama-netw-open/"}]}}