调控调节性 T 细胞：这是解锁胰腺导管腺癌有效免疫治疗的关键吗？

The five-year survival rates for pancreatic ductal adenocarcinoma (PDAC) have scarcely improved over the last half-century. It is inherently resistant to FDA-approved immunotherapies, which have transformed the outlook for patients with other advanced solid tumours.

Accumulating evidence relates this resistance to its hallmark immunosuppressive milieu, which instils progressive dysfunction among tumour-infiltrating effector T cells. This milieu is established at the inception of neoplasia by immunosuppressive cellular populations, including regulatory T cells (T regs ), which accumulate in parallel with the progression to malignant PDAC.

Thus, the therapeutic manipulation of T regs has captured significant scientific and commercial attention, bolstered by the discovery that an abundance of tumour-infiltrating T regs correlates with a poor prognosis in PDAC patients.

Herein, we propose a mechanism for the resistance of PDAC to anti-PD-1 and CTLA-4 immunotherapies and re-assess the rationale for pursuing T reg -targeted therapies in light of recent studies that profiled the immune landscape of patient-derived tumour samples.

We evaluate strategies that are emerging to limit T reg -mediated immunosuppression for the treatment of PDAC, and signpost early-stage trials that provide preliminary evidence of clinical activity. In this context, we find a compelling argument for investment in the ongoing development of T reg -targeted immunotherapies for PDAC.