Tumor-reactive LAG3+CD8+ T cells diverge into terminally exhausted cells and long-lived memory T cells.

LAG3+CD8+ tumor-reactive T cells differentiate into terminally exhausted and long-lived memory cells, with the latter essential for sustained anti-tumor immunity.

• Why it matters: Understanding T cell exhaustion and memory formation is crucial for improving immunotherapies against tumors and chronic infections, yet the origins and roles of different exhausted T cell subsets remain unclear.
• What they did: Using a Lag3 lineage-tracing mouse model, the study identified two tumor-specific CD8+ T cell subsets distinguished by LAG3 expression, sharing TCR clonotypes but differing in location, function, and transcriptional profile.
• The result: The findings reveal that LAG3- progenitor T cells persist and are vital for anti-tumor memory, suggesting that targeting LAG3+ exhausted cells could enhance durable immune responses.