胰腺导管腺癌免疫检查点阻断耐药的生物标志物和治疗选择

Biomarkers and treatment options for immune checkpoint blockade resistance in pancreatic ductal adenocarcinoma

摘要:

免疫检查点阻断（immune checkpoint blockade，ICB）的单药治疗在胰腺导管腺癌（pancreatic ductal adenocarcinoma，PDAC）中未见成效，采取合理的联合疗法是克服PDAC ICB抵抗的有效策略。目前为克服PDAC ICB耐药的联合手段主要包括增强PDAC表面的程序性死亡受体-配体1（programmed cell death-ligand 1，PD-L1）或组织相容性复合体Ⅰ（histocompatibility complex Ⅰ，MHC-Ⅰ）；靶向免疫细胞中发挥抑制功能的关键效应因子，改善PDAC的免疫抑制微环境；联合能量消融、光动力疗法、纳米材料包裹等手段促进肿瘤相关抗原的释放，刺激免疫激活。本综述旨在对近年PDAC中发现的ICB耐药靶标和新兴手段进行梳理，为克服PDAC ICB耐药提供新思路。

Abstract:

Monotherapy for immune checkpoint blockade（ICB） lacks efficacy in pancreatic ductal adenocarcinoma（PDAC），and rational combination therapy is an effective strategy to overcome ICB resistance in PDAC. Currently，combination therapies to overcome ICB resistance in PDAC mainly include the following：enhanced expression of programmed death receptor-ligand 1 or histocompatibility complex Ⅰ on the surface of PDAC cells；targeting key effectors in immune cells that play an immunosuppressive function to improve the immunosuppressive microenvironment of PDAC；combining the methods such as energy ablation，photodynamic therapy，and nano-material encapsulation to promote the release of tumor-associated antigens and stimulate immune activation. This article reviews the targets for ICB resistance and emerging methods in PDAC in recent years，so as to provide new ideas to address ICB resistance in PDAC.