Myeloid reprogramming generates myeloid-derived activating cells to potentiate radiotherapy and suppress metastasis.

Myeloid-specific Tet2 deletion generates myeloid-derived activating cells that enhance radiotherapy and suppress metastasis in lung cancer models.

• Why it matters: Radiation-induced immunosuppressive myeloid cells contribute to therapeutic resistance and metastasis, limiting the effectiveness of radiotherapy and immunotherapy in cancer treatment.
• What they did: The study used genetic deletion and pharmacological inhibition of TET2 in mice, along with spatiotemporal mapping, to show that Tet2 loss redirects monocyte differentiation toward immunogenic MDACs and enhances antitumor immune responses.
• The result: TET2 inhibition improves radiotherapy and PD-L1 blockade efficacy, controlling primary and metastatic tumors, and suggests myeloid reprogramming as a strategy to enhance cancer immunotherapy outcomes.