肿瘤浸润 CD8+T 细胞与肿瘤相关 CD68+巨噬细胞联合预测可切除胃癌的术后预后和辅助化疗获益。
Tumor-infiltrating CD8+ T cells combined with tumor-associated CD68+ macrophages predict postoperative prognosis and adjuvant chemotherapy benefit in resected gastric cancer.
机构信息
Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
出版信息
BMC Cancer. 2019 Sep 14;19(1):920. doi: 10.1186/s12885-019-6089-z.
BACKGROUND
Tumor-infiltrating immune cells are present in various malignant tumors, but their clinical significance in gastric cancer (GC) remains unclear. This study aimed to investigate the prognostic significance of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs).
METHODS
Using a prospective database containing 401 cases of GC, we evaluated TIL (cluster of differentiation 8 (CD8) expression) and TAM (cluster of differentiation 68 (CD68) expression) statuses via immunohistochemical staining.
RESULTS
Compared with CD8+ TIL-negative cases (n = 196, 48.6%), CD8+ TIL-positive cases (n = 205, 51.1%) showed significantly better recurrence-free survival (RFS) [log-rank p<0.001; multivariate HR: 0.372; 95% confidence interval (CI): 0.239-0.579, p<0.001]. In contrast, compared with CD68+ TAM-negative cases (n = 217, 54.1%), CD68+ TAM-positive cases (n = 184, 45.9%) had significantly poor RFS [log-rank p<0.001; multivariate HR: 2.182; 95% CI: 1.435-3.318, p<0.001]. Thus, patients with a positive CD8+ TIL and negative CD68+ TAM status exhibited significantly increased RFS. Multivariate analysis demonstrated that CD8+ TILs and CD68+ TAMs may serve as independent prognostic markers for RFS. Incorporating CD8+ TIL and CD68+ TAM statuses into the AJCC TNM system generated a predictive model with better predictive accuracy for RFS. More importantly, patients with a positive TIL and negative TAM status showed a tendency of improved RFS after postoperative adjuvant chemotherapy (PAC). Similar results were obtained by overall survival (OS) analysis.
CONCLUSIONS
CD8+ TIL and CD68+ TAM statuses were identified as independent prognostic factors that may be integrated into the current TNM staging system to refine risk stratification and to better predict the survival benefit from PAC in patients with GC.
TRIAL REGISTRATION
The current controlled trial was registered at ClinicalTrials.gov (ID: NCT02327481 ) on December 30, 2014.
背景
肿瘤浸润免疫细胞存在于各种恶性肿瘤中，但它们在胃癌（GC）中的临床意义尚不清楚。本研究旨在探讨肿瘤浸润淋巴细胞（TIL）和肿瘤相关巨噬细胞（TAM）的预后意义。
方法
使用包含 401 例 GC 病例的前瞻性数据库，我们通过免疫组织化学染色评估 TIL（分化群 8（CD8）表达）和 TAM（分化群 68（CD68）表达）状态。
结果
与 CD8+TIL 阴性病例（n=196，48.6%）相比，CD8+TIL 阳性病例（n=205，51.1%）的无复发生存率（RFS）明显更好[对数秩 p<0.001；多变量 HR：0.372；95%置信区间（CI）：0.239-0.579，p<0.001]。相比之下，与 CD68+TAM 阴性病例（n=217，54.1%）相比，CD68+TAM 阳性病例（n=184，45.9%）的 RFS 明显较差[对数秩 p<0.001；多变量 HR：2.182；95%CI：1.435-3.318，p<0.001]。因此，具有阳性 CD8+TIL 和阴性 CD68+TAM 状态的患者 RFS 明显增加。多变量分析表明，CD8+TIL 和 CD68+TAMs 可能是 RFS 的独立预后标志物。将 CD8+TIL 和 CD68+TAM 状态纳入 AJCC TNM 系统可生成具有更高预测准确性的 RFS 预测模型。更重要的是，术后辅助化疗（PAC）后具有阳性 TIL 和阴性 TAM 状态的患者 RFS 有改善趋势。OS 分析也得到了类似的结果。
结论
CD8+TIL 和 CD68+TAM 状态被确定为独立的预后因素，可纳入当前的 TNM 分期系统，以细化风险分层，并更好地预测 GC 患者从 PAC 中获得生存获益。
试验注册
本对照试验于 2014 年 12 月 30 日在 ClinicalTrials.gov（ID：NCT02327481）注册。
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