Division of Surgical Oncology, Department of Surgery, University of California, Davis, Sacramento, California, USA.
Department of Pathology and Laboratory Medicine, UC Davis Medical Center, Sacramento, California, USA.
J Surg Oncol. 2024 Apr;129(5):885-892. doi: 10.1002/jso.27581. Epub 2024 Jan 9.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor response to systemic therapies, including immunotherapy. Given the immunotherapeutic potential of natural killer (NK) cells, we evaluated intratumoral NK cell infiltrates along with cytotoxic T cells in PDAC to determine their association with patient outcomes.
We analyzed tumors from 93 PDAC patients treated from 2012 to 2020. Predictor variables included tumor-infiltrating lymphocytes (TILs), T-cell markers (CD3, CD8, CD45RO), NK marker (NKp46), and NK inhibitory marker (major histocompatibility complex class I [MHC-I]) by immunohistochemistry. Primary outcome variables were recurrence-free survival (RFS) and overall survival (OS).
Mean TILs, CD3, and NKp46 scores were 1.3 ± 0.63, 20.6 ± 17.5, and 3.1 ± 3.9, respectively. Higher expression of CD3 and CD8 was associated with higher OS, whereas NK cell infiltration was not associated with either RFS or OS. There was a tight positive correlation between MHC-I expression and all T-cell markers, but not with NKp46.
Overall NK cell infiltrates were low in PDAC and did not predict clinical outcomes, whereas T-cell infiltrates did. Further characterization of the immune infiltrate in PDAC, including inhibitory signals and suppressive cell types, may yield better biomarkers of prognosis and immune targeting in this refractory disease.
胰腺导管腺癌（PDAC）是一种侵袭性癌症，对包括免疫疗法在内的全身治疗反应不佳。鉴于自然杀伤（NK）细胞的免疫治疗潜力，我们评估了 PDAC 中的肿瘤内 NK 细胞浸润以及细胞毒性 T 细胞，以确定它们与患者结局的关系。
我们分析了 2012 年至 2020 年期间治疗的 93 例 PDAC 患者的肿瘤。预测变量包括肿瘤浸润淋巴细胞（TILs）、T 细胞标志物（CD3、CD8、CD45RO）、NK 标志物（NKp46）和 NK 抑制性标志物（主要组织相容性复合体 I [MHC-I]），通过免疫组织化学进行评估。主要结局变量是无复发生存（RFS）和总生存（OS）。
平均 TILs、CD3 和 NKp46 评分分别为 1.3±0.63、20.6±17.5 和 3.1±3.9。CD3 和 CD8 的高表达与更高的 OS 相关，而 NK 细胞浸润与 RFS 或 OS 均无关。MHC-I 表达与所有 T 细胞标志物之间存在紧密的正相关，但与 NKp46 无关。
PDAC 中的总体 NK 细胞浸润较低，与临床结局无关，而 T 细胞浸润则与临床结局相关。进一步对 PDAC 中的免疫浸润进行特征描述，包括抑制性信号和抑制性细胞类型，可能会为这种难治性疾病提供更好的预后和免疫靶向生物标志物。
