Laboratory of Molecular Medicine, Division of Cancer Research, Regional Cancer Centre (Research Centre, University of Kerala), Thiruvananthapuram, Kerala, 695011, India.
Division of Surgical Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala, 695011, India.
Clin Exp Med. 2023 Jul;23(3):859-869. doi: 10.1007/s10238-022-00852-x. Epub 2022 Jul 9.
Antitumor immune evasion is a hallmark for the development and progression of cancer. Tumor cells adopt various mechanisms to escape the host immune system recognition. One such mechanism is the over expression of programmed death ligand (PD-L1), a negative T cell regulatory molecule. Because PD-L1 overexpression causes resistance to chemotherapeutic response in many cancers, herein we explored the relationship between PD-L1 and multidrug resistance protein MDR1 in breast cancer. Immunohistochemical evaluation of PD-L1 and MDR1 proteins in 194 breast cancer tissue samples were carried out. The relationship between PD-L1 and MDR1 expression on cancer cells with clinicopathological factors and prognosis was investigated. IHC showed a significant correlation between PD-L1 and MDR1 expression on tumor cells. Increased PD-L1 expression was also associated with lymph node status and tumor grade of the patient. Our results also revealed that the expression of PD-L1 and MDR1 was higher in TNBC subtype compared to other breast cancer subtypes. Therefore, a better understanding of the molecular mechanism through which PD-1/PD-L1 pathway contribute to the chemoresistance might bring forth the prognostic significance of PD-L1 and selection of patients who may benefit from immunotherapy.
肿瘤免疫逃逸是癌症发生和发展的标志。肿瘤细胞采用各种机制来逃避宿主免疫系统的识别。其中一种机制是程序性死亡配体 1(PD-L1)的过度表达,PD-L1 是一种负性 T 细胞调节分子。由于 PD-L1 的过度表达导致许多癌症对化疗反应产生耐药性,因此我们在此探讨了 PD-L1 与乳腺癌中多药耐药蛋白 MDR1 之间的关系。对 194 例乳腺癌组织样本中的 PD-L1 和 MDR1 蛋白进行了免疫组织化学评估。研究了癌细胞中 PD-L1 和 MDR1 表达与临床病理因素和预后之间的关系。免疫组化显示肿瘤细胞上 PD-L1 和 MDR1 表达之间存在显著相关性。PD-L1 表达增加也与患者的淋巴结状态和肿瘤分级相关。我们的结果还表明,在三阴性乳腺癌亚型中,PD-L1 和 MDR1 的表达高于其他乳腺癌亚型。因此,更好地了解 PD-1/PD-L1 通路在化疗耐药中的分子机制可能会揭示 PD-L1 的预后意义,并选择可能受益于免疫治疗的患者。