PD-1/PD-L1 expression in pancreatic cancer and its implication in novel therapies.
PD-1/PD-L1 expression in pancreatic cancer and its implication in novel therapies.
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DOI：
10.15386/mpr-2116
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发表时间：
2021-10
影响因子：
--
通讯作者：
Mircea, Petru Adrian
中科院分区：
文献类型：
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作者：
Mucileanu, Adrian;Chira, Romeo;Mircea, Petru Adrian
胰腺癌是发达国家第七大死因，尽管过去20年进行了大量研究，但其预后仍然较差。免疫疗法是癌症治疗中相对较新的策略。免疫治疗的目的是阻断肿瘤细胞的免疫抑制作用。 PD1/PD-L1 轴在效应 T 细胞的抑制和调节性 T 细胞 (Treg) 的发育中发挥重要作用。阻断这些检查点以及抑制信号，会导致 Tregs 凋亡，并增强效应 T 细胞针对肿瘤抗原的免疫反应。不幸的是，胰腺癌通常被认为是一种非免疫原性肿瘤。因此，除了一些患有 MSI/dMMR（微卫星不稳定性/错配修复缺陷）的患者外，PD-1/PD-L1 抑制剂在胰腺癌中表现出较差的效果。此外，胰腺癌具有特殊的微环境，强烈的促纤维增生反应、间质液压力升高、缺氧条件和细胞外pH呈酸性，促进肿瘤的发生和进展。错配修复缺陷 (dMMR) 与高水平的突变相关新抗原相关，这些新抗原大多数被免疫细胞识别，可以预测对抗 PD-1/PD-L1 治疗的良好反应。 PD-1/PD-L1 分子也可以以可溶形式存在（sPD-1、sPD-L1）。这些分子在胰腺癌的预后和治疗中具有潜在作用。
Pancreatic cancer is the seventh leading cause of death in developed countries and it still has a poor prognosis despite intense research in the last 20 years. Immunotherapy is a relatively new strategy in cancer treatment. The aim of immunotherapy is to block the immunosuppressive effect of tumoral cells. The PD1/PD-L1 axis has an important role in the inhibition of effector T cells and the development of regulatory T cells (Tregs). Blocking these checkpoints, and also inhibitory signals, leads to apoptosis of Tregs and increased immune response of effector T cells against tumoral antigens. Unfortunately, pancreatic cancer is generally considered to be a non-immunogenic tumor. Thus PD-1/PD-L1 inhibitors demonstrated poor results in pancreatic cancer, excepting some patients with MSI/dMMR (microsatellite instability/deficient mismatch repair). Furthermore, pancreatic cancer has a particular microenvironment with a strong desmoplastic reaction, increased interstitial fluid pressure, hypoxic conditions, and acidic extracellular pH, which promote tumorigenesis and progression of the tumor. Mismatch repair deficiency (dMMR) is correlated with a high level of mutation-associated neoantigens, most recognized by immune cells which could predict a favorable response to anti-PD-1/PD-L1 therapy. PD-1/PD-L1 molecules could be also found as soluble forms (sPD-1, sPD-L1). These molecules have a potential role in the prognosis and treatment of pancreatic cancer.