Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD.
J Immunol. 2023 Apr 1;210(7):859-868. doi: 10.4049/jimmunol.2200660.
Advances in cancer immunotherapy, particularly immune checkpoint inhibitors, have dramatically improved the prognosis for patients with metastatic melanoma and other previously incurable cancers. However, patients with pancreatic ductal adenocarcinoma (PDAC) generally do not respond to these therapies. PDAC is exceptionally difficult to treat because of its often late stage at diagnosis, modest mutation burden, and notoriously complex and immunosuppressive tumor microenvironment. Simultaneously interrogating features of cancer, immune, and other cellular components of the PDAC tumor microenvironment is therefore crucial for identifying biomarkers of immunotherapeutic resistance and response. Notably, single-cell and multiomics technologies, along with the analytical tools for interpreting corresponding data, are facilitating discoveries of the systems-level cellular and molecular interactions contributing to the overall resistance of PDAC to immunotherapy. Thus, in this review, we will explore how multiomics and single-cell analyses provide the unprecedented opportunity to identify biomarkers of resistance and response to successfully sensitize PDAC to immunotherapy.
癌症免疫疗法的进展,特别是免疫检查点抑制剂,显著改善了转移性黑色素瘤和其他以前无法治愈的癌症患者的预后。然而,胰腺导管腺癌 (PDAC) 患者通常对这些疗法没有反应。由于 PDAC 通常在诊断时已处于晚期、突变负担适中,以及众所周知的复杂和免疫抑制的肿瘤微环境,因此治疗起来异常困难。因此,同时检测 PDAC 肿瘤微环境中的癌症、免疫和其他细胞成分的特征对于确定免疫治疗耐药和反应的生物标志物至关重要。值得注意的是,单细胞和多组学技术以及用于解释相应数据的分析工具,正在促进对导致 PDAC 整体免疫治疗耐药的系统水平细胞和分子相互作用的发现。因此,在这篇综述中,我们将探讨多组学和单细胞分析如何提供前所未有的机会来识别对免疫治疗的耐药和反应的生物标志物,以成功地使 PDAC 对免疫治疗敏感。