
組織常在性 NK 細胞は、cDC1-CD8 T 細胞の活性化を促進することで、膵臓がんの生存率を向上させる。


coremsg

The immunosuppressive microenvironment in pancreatic ductal adenocarcinoma (PDAC) prevents tumor control and strategies to restore anti-cancer immunity (i.e. by increasing CD8 T cell activity) have had limited success. Here we demonstrate how inducing localized physical damage using ionizing radiation (IR) unmasks the benefit of immunotherapy by increasing tissue-resident NK (trNK) cells that support CD8 T activity. Our data confirms that targeting mouse orthotopic PDAC tumors with IR together with CCR5 inhibition and PD1 blockade reduces E-cadherin positive tumor cells by recruiting a hypoactive NKG2D-ve NK population, phenotypically reminiscent of trNK cells, that supports CD8 T cell involvement. We show an equivalent population in human PDAC cohorts that represents immunomodulatory trNK cells that could similarly support CD8 T cell levels in a cDC1-dependent manner. Importantly, a trNK signature associates with survival in PDAC and solid malignancies revealing a potential beneficial role for trNK in improving adaptive anti-tumor responses and supporting CCR5i/αPD1 and IR-induced damage as a novel therapeutic approach.

### Competing Interest Statement

The authors have declared no competing interest.

Tissue-resident NK cells support survival in pancreatic cancer through promotion of cDC1-CD8T activity

膵臓がんにおける組織常在性-nk-細胞による-cd8-t-細胞活性の促進を通じた生存率の向上


膵臓がんにおける組織常在性 NK 細胞による CD8 T 細胞活性の促進を通じた生存率の向上
