背景:胰腺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。它的特点是大部分免疫抑制的环境,功能失调的免疫细胞和活跃的免疫抑制途径,有利于肿瘤逃避和进展。因此,对肿瘤微环境和各种细胞亚型及其功能能力的研究和理解对于实现更有效的治疗至关重要,尤其是使用新的免疫疗法。
方法:使用免疫组织化学方法分析了70例胰腺腺癌分为两组,其中43例可切除疾病和27例不可切除疾病,关于程序性细胞死亡配体1(PD-L1)的表达,程序性细胞死亡配体2(PD-L2),和人类白细胞抗原G(HLA-G)分子以及CD4和CD8T淋巴细胞的群体,调节性T细胞(Tregs),和M2巨噬细胞(MM2)。几个统计检验,包括多变量分析,进行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。
结果:CD8+T淋巴细胞和M2巨噬细胞在手术组中占主导地位,PD-L2表达在不可切除组中占主导地位。PD-L2与T分期相关,淋巴结转移,和临床分期,而在生存分析中,PD-L2和HLA-G与较短的生存期相关。在无法手术的情况下,Tregs细胞,MM2、PD-L1、PD-L2和HLA-G呈正相关。
结论:在所研究的病例中,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,主要是不能切除的病变,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。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.