Grow immune command posts inside tumours
Tumours that contain small immune structures resembling lymph nodes respond far better to immunotherapy. Inducing those structures on purpose could make cold tumours responsive.
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.
- Cold tumours and the immunosuppressive microenvironment · Most tumours keep the immune system out or asleep, so immunotherapy helps only a minority.
- No one can predict who responds to immunotherapy · Checkpoint drugs cure some patients and do nothing for most. We still cannot tell the two apart before treating.
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