Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul.
Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul.
ESMO Open. 2024 Nov;9(11):103969. doi: 10.1016/j.esmoop.2024.103969. Epub 2024 Nov 6.
The assessment of tumor-infiltrating lymphocytes (TILs) has led to the development of various immunotherapies beyond their predictive potential in gastrointestinal malignancies. However, the clinicopathologic and prognostic values of TILs have yet to be well elucidated in distal extrahepatic bile duct carcinoma (DBDC).
We evaluated stromal TILs (sTILs) and intraepithelial TILs (iTILs) in 405 surgically resected DBDCs to analyze their correlations with overall survival (OS) and recurrence-free survival (RFS) and with clinicopathologic parameters according to the eighth edition of the American Joint Committee on Cancer scheme.
High levels of sTIL density (sTIL; >5%) and iTIL count (iTIL; >3) were found in 245 (61%) and 74 cases (18%), respectively. sTIL was more commonly found in larger tumors (P = 0.048) diffusely involving both intra- and extrapancreatic bile ducts (P = 0.013), in tumors with lower T category (P = 0.002), and in tumors without pancreatic (P = 0.003) or duodenal invasion (P < 0.001). iTIL was associated with tumors with papillary or nodular growth pattern (P < 0.001) without perineural invasion (P = 0.006). Both sTIL and iTIL significantly predicted better OS (P = 0.009 and 0.036, respectively) and RFS (P = 0.003 and 0.026, respectively). sTIL consistently provided prognostic predictability in OS, even when tested with different quantitative cut-offs and prognostically stratified OS (P = 0.006) and RFS (P = 0.005) on multivariate analysis. The survival benefit of sTIL persisted regardless of the stage in both OS (P = 0.010 for lower stages I and II and P = 0.001 for higher stages III and IV) and RFS (P = 0.004 and 0.025 for lower- and higher-stage tumors, respectively).
sTILs were superior to iTILs in predicting survival, and it was shown to be a strong prognosticator for DBDC patients regardless of the stage. The utility of sTILs may extend beyond prognostication to aid in predicting therapeutic responses in DBDC patients.
肿瘤浸润淋巴细胞（TILs）的评估已经导致了各种免疫疗法的发展，超出了其在胃肠道恶性肿瘤中的预测潜力。然而，TILs 的临床病理和预后价值在远端肝外胆管癌（DBDC）中尚未得到很好的阐明。
我们评估了 405 例手术切除的 DBDC 中的基质 TILs（sTILs）和上皮内 TILs（iTILs），以分析它们与总生存（OS）和无复发生存（RFS）的相关性，并根据第八版美国癌症联合委员会（AJCC）方案与临床病理参数相关。
在 245 例（61%）和 74 例（18%）中发现高 sTIL 密度（sTIL；>5%）和 iTIL 计数（iTIL；>3）。sTIL 在更大的肿瘤中更为常见（P=0.048），广泛累及胰内和胰外胆管（P=0.013），在 T 分期较低的肿瘤中（P=0.002），以及无胰腺（P=0.003）或十二指肠侵犯的肿瘤中（P<0.001）。iTIL 与具有乳头状或结节状生长模式的肿瘤相关（P<0.001），无神经周围侵犯（P=0.006）。sTIL 和 iTIL 均显著预测更好的 OS（P=0.009 和 0.036）和 RFS（P=0.003 和 0.026）。sTIL 在 OS 的多变量分析中，即使使用不同的定量截止值和预后分层 OS（P=0.006）和 RFS（P=0.005）进行测试，也始终提供了预后预测能力。无论在 OS（P=0.010 用于较低分期 I 和 II，P=0.001 用于较高分期 III 和 IV）还是 RFS（P=0.004 和 0.025 用于较低和较高分期肿瘤）中，sTIL 的生存获益均持续存在。
sTILs 在预测生存方面优于 iTILs，并且无论分期如何，它都是 DBDC 患者的强有力预后指标。sTILs 的应用范围可能不仅限于预后，还可以帮助预测 DBDC 患者的治疗反应。
