Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", 80131 Naples, Italy.
Unit of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, 37019 Verona, Italy.
Cells. 2022 Oct 22;11(21):3340. doi: 10.3390/cells11213340.
Pancreatic ductal adenocarcinoma (PDAC) is currently the most deadly cancer. Although characterized by 5-20% of neoplastic cells in the highly fibrotic stroma, immunotherapy is not a valid option in PDAC treatment. As CXCR4-CXCL12 regulates tumor invasion and T-cell access and PD-1/PD-L1 controls immune tolerance, 76 PDACs were evaluated for CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in the epithelial and stromal component. Neoplastic CXCR4 and CXCL12 discriminated PDACs for recurrence-free survival (RFS), while CXCL12 and CXCR7 discriminated patients for cancer-specific survival (CSS). Interestingly, among patients with radical resection (R0), high tumor CXCR4 clustered patients with worse RFS, high CXCL12 identified poor prognostic patients for both RFS and CSS, while stromal lymphocytic-monocytic PD-L1 associated with improved RFS and CSS. PD-1 was only sporadically expressed (<1%) in focal lymphocyte infiltrate and does not impact prognosis. In multivariate analysis, tumoral CXCL12, perineural invasion, and AJCC lymph node status were independent prognostic factors for RFS; tumoral CXCL12, AJCC Stage, and vascular invasion were independent prognostic factors for CSS. CXCL12's poor prognostic meaning was confirmed in an additional perspective-independent 13 fine-needle aspiration cytology advanced stage-PDACs. Thus, CXCR4-CXCL12 evaluation in PDAC identifies prognostic categories and could orient therapeutic approaches.
胰腺导管腺癌（PDAC）目前是最致命的癌症。尽管在高度纤维化的基质中有 5-20%的肿瘤细胞，但免疫疗法并不是 PDAC 治疗的有效选择。由于 CXCR4-CXCL12 调节肿瘤侵袭和 T 细胞浸润，PD-1/PD-L1 控制免疫耐受，因此评估了 76 例 PDAC 上皮和基质成分中的 CXCR4-CXCL12-CXCR7 和 PD-1/PD-L1。肿瘤 CXCR4 和 CXCL12 可区分 PDAC 患者的无复发生存率（RFS），而 CXCL12 和 CXCR7 可区分患者的癌症特异性生存率（CSS）。有趣的是，在根治性切除（R0）的患者中，高肿瘤 CXCR4 使 RFS 较差的患者聚类，高 CXCL12 确定了 RFS 和 CSS 预后不良的患者，而基质淋巴细胞单核细胞 PD-L1 与 RFS 和 CSS 改善相关。PD-1 在局灶性淋巴细胞浸润中仅零星表达（<1%），不影响预后。多变量分析表明，肿瘤 CXCL12、神经周围侵犯和 AJCC 淋巴结状态是 RFS 的独立预后因素；肿瘤 CXCL12、AJCC 分期和血管侵犯是 CSS 的独立预后因素。在另一个独立的、前瞻性的 13 例细针穿刺细胞学晚期 PDAC 中证实了 CXCL12 的不良预后意义。因此，PDAC 中 CXCR4-CXCL12 的评估可确定预后类别，并可指导治疗方法。
