胰腺腺癌中的免疫细胞和检查点:与临床和病理特征的关联。
Immune cells and checkpoints in pancreatic adenocarcinoma: Association with clinical and pathological characteristics.
发表日期:2024
作者:
Maria Auxiliadora de Paula Carneiro Cysneiros, Magno Belém Cirqueira, Lucas de Figueiredo Barbosa, Ênio Chaves de Oliveira, Lucio Kenny Morais, Isabela Jubé Wastowski, Vitor Gonçalves Floriano
来源:
Cell Death & Disease
摘要:
胰腺癌是一种极具侵袭性的肿瘤,为了实现真正有效的治疗,需要克服许多挑战。其特点是大部分免疫抑制环境,免疫细胞功能失调和活跃的免疫抑制途径有利于肿瘤逃避和进展。因此,研究和了解肿瘤微环境和各种细胞亚型及其功能对于实现更有效的治疗至关重要,特别是使用新的免疫疗法。 70 例胰腺癌分为两组,其中 43 例患有可切除疾病,27 例患有可切除疾病使用免疫组织化学方法分析患有不可切除疾病的人程序性细胞死亡配体 1 (PD-L1)、程序性细胞死亡配体 2 (PD-L2) 和人白细胞抗原 G (HLA-G) 分子以及群体的表达CD4 和 CD8 T 淋巴细胞、调节性 T 细胞 (Treg) 和 M2 巨噬细胞 (MM2)。进行了包括多变量分析在内的多项统计测试,以检查这些免疫细胞和免疫抑制分子如何影响胰腺腺癌的演变和预后。手术组中以 CD8 T 淋巴细胞和 M2 巨噬细胞为主,不可切除组中以 PD-L2 表达为主团体。 PD-L2与T分期、淋巴结转移和临床分期相关,而在生存分析中,PD-L2和HLA-G与较短的生存期相关。在无法手术的病例中,Treg细胞、MM2、PD-L1、PD-L2和HLA-G呈正相关。在研究的病例中,PD-L2和HLA-G表达与较差的生存率相关。肿瘤微环境的特点是耐受和免疫抑制模式,主要是在不可切除的病变中,在免疫抑制细胞和肿瘤细胞表达的免疫检查点蛋白之间观察到广泛的积极影响。版权所有:© 2024 Cysneiros 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章,允许在任何媒体上不受限制地使用、分发和复制,前提是注明原始作者和来源。
Pancreatic adenocarcinoma is an extremely aggressive neoplasm, with many challenges to be overcome in order to achieve a truly effective treatment. It is characterized by a mostly immunosuppressed environment, with dysfunctional immune cells and active immunoinhibitory pathways that favor tumor evasion and progression. Thus, the study and understanding of the tumor microenvironment and the various cells subtypes and their functional capacities are essential to achieve more effective treatments, especially with the use of new immunotherapeutics.Seventy cases of pancreatic adenocarcinoma divided into two groups 43 with resectable disease and 27 with unresectable disease were analyzed using immunohistochemical methods regarding the expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), and human leukocyte antigen G (HLA-G) molecules as well as the populations of CD4+ and CD8+ T lymphocytes, regulatory T cells (Tregs), and M2 macrophages (MM2). Several statistical tests, including multivariate analyses, were performed to examine how those immune cells and immunoinhibitory molecules impact the evolution and prognosis of pancreatic adenocarcinoma.CD8+ T lymphocytes and M2 macrophages predominated in the group operated on, and PD-L2 expression predominated in the unresectable group. PD-L2 was associated with T stage, lymph node metastasis, and clinical staging, while in survival analysis, PD-L2 and HLA-G were associated with a shorter survival. In the inoperable cases, Tregs cells, MM2, PD-L1, PD-L2, and HLA-G were positively correlated.PD-L2 and HLA-G expression correlated with worse survival in the cases studied. Tumor microenvironment was characterized by a tolerant and immunosuppressed pattern, mainly in unresectable lesions, where a broad positive influence was observed between immunoinhibitory cells and immune checkpoint proteins expressed by tumor cells.Copyright: © 2024 Cysneiros et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.