A myeloid mechanical immune checkpoint suppresses T-cell activation through CD209–ICAM-2–ERM signalling

Using human CD209-knockin mice, we treated the MC38 subcutaneous tumors with the control antibody and the C209 neutralizing antibody respectively. After obtaining the tumor tissues, we prepared single-cell suspensions and conducted single-cell sequencing to analyze the infiltration changes of immune cells in the tumor microenvironment.

We show that blockade of human CD209 with a neutralizing antibody or a humanized antibody enhances T-cell infiltration and activation, leading to tumour regression across multiple models. These findings reveal a myeloid-driven mechanical checkpoint that regulates T-cell activation and immune evasion and establish CD209 as a promising immunotherapeutic target.