McLoughlin Kaitlin C, Brown Zachary J, Shukla Yashvita, Shukla Vivek
TOSB, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA.
Department of Surgery, School of Medicine, University of Colorado, Denver, CO 80045, USA.
Discov Med. 2018 Sep;26(142):85-92.
A growing understanding of the immune system and its anti-tumor functions has been imperative for the comprehension of malignant processes and beneficial in the pursuit of effective cancer treatments. To defend the body, immune cells must be able to differentiate between self and foreign cells using checkpoints, allowing the immune cells to attack foreign cells. Among the different types of immune target therapies recently developed, checkpoint inhibitors have come to the forefront in cancer treatment, encouraging their study in numerous different types of cancer, including hepato-pancreato-biliary malignancies (HPB). Traditionally, these malignancies have been treated with standard cytotoxic chemotherapy, but with little benefit in the metastatic setting. However, impressive results with checkpoint inhibitor therapy have been noted in a number of cancers as these agents enable immune cells to kill cancer cells more efficiently. Two classes of checkpoint inhibitors being extensively studied are inhibitors of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) ligand and programmed cell death protein 1 and its ligand (PD-1 and PD-L1). Checkpoint inhibitors have an advantage over other types of immunotherapies, such as cell-based therapies, in that they are commercially available and can be given to patients with a range of pathologies and regardless of HLA status. Herein, we will discuss the application of immune checkpoint inhibitors to HPB malignancies as well as the limitations of these medications in these cancers.
对免疫系统及其抗肿瘤功能的认识不断加深，对于理解恶性肿瘤过程至关重要，并且有助于寻求有效的癌症治疗方法。为了保护身体，免疫细胞必须能够利用检查点区分自身细胞和外来细胞，从而使免疫细胞能够攻击外来细胞。在最近开发的不同类型的免疫靶向治疗中，检查点抑制剂在癌症治疗中脱颖而出，促使人们对包括肝胰胆恶性肿瘤（HPB）在内的多种不同类型癌症进行研究。传统上，这些恶性肿瘤采用标准的细胞毒性化疗进行治疗，但在转移性情况下获益甚微。然而，在许多癌症中，检查点抑制剂治疗取得了令人瞩目的结果，因为这些药物能使免疫细胞更有效地杀死癌细胞。目前正在广泛研究的两类检查点抑制剂是细胞毒性T淋巴细胞相关蛋白4（CTLA-4）配体抑制剂以及程序性细胞死亡蛋白1及其配体（PD-1和PD-L1）抑制剂。检查点抑制剂相对于其他类型的免疫疗法（如基于细胞的疗法）具有优势，因为它们已商业化，并且可以用于患有多种疾病的患者，而无需考虑HLA状态。在此，我们将讨论免疫检查点抑制剂在HPB恶性肿瘤中的应用以及这些药物在这些癌症中的局限性。
