Romano Fabrizio, Cesana Giovanni, Caprotti Roberto, Bovo Giorgio, Uggeri Fabio, Piacentini Maria Gaia, Crippa Stefano, Uggeri Franco
Department of General Surgery (Chirurgia I), San Gerardo Hospital II University of Milan-Bicocca, Monza, Italy.
Hepatogastroenterology. 2006 Jul-Aug;53(70):634-8.
BACKGROUND/AIMS: Tumor infiltrating lymphocytes (TILs), recognized as a tumor-host reaction, have been linked to prognosis in various tumors, with a clear positive correlation between the density of the lymphoid infiltrate at the advancing margin of the tumor and the prognosis of the patients. TILs are somewhat activated by tumor associated antigens and by IL-2 endogenous release. The aim of this study is to verify if subcutaneously administered IL-2 is able to enhance TILs in gastric cancer patients and is able to influence the prognosis of the patients.
We enrolled 39 consecutive patients with gastric adenocarcinoma. Patients were randomized to be treated with surgery alone (control group, 20 patients) or with surgery plus preoperative IL-2 (Interleukin-2) administration (treated group, 19 patients). Total lymphocytes, CD4 and CD4/CD8 were evaluated pre- and postoperatively. Peritumoral stromal reaction, neutrophils, lymphocytes and eosinophils infiltration in tumor histology were evaluated as well as survival curves and compared between the groups.
IL-2 treatment was safe and well tolerated, and in the IL-2 treated group a significant increase over the baseline pretreatment values of the total lymphocyte, CD4 and CD4/CD8 on both the 14th and 50th postoperative days was observed (p < 0.05). Peritumoral stromal reaction, neutrophils and eosinophils infiltration did not shown any statistical difference between the two groups. Otherwise we observed a statistically significant difference in the peri- and intratumoral lymphocytes infiltration between IL-2 treated and control patients (p = 0.000026). Median overall and disease-free survivals were longer, even if not significantly, in the IL-2 group than in the control arm (p = 0.089 and p = 0.09 respectively).
Our data shows that IL-2 seems to be able to induce substantial changes in the inflammatory infiltration of the neoplasm, improving the host activity toward the tumor and enhancing the TILs phenomenon in gastric cancer patients. This feature seems to improve the prognosis of the patients.
背景/目的：肿瘤浸润淋巴细胞（TILs）被认为是一种肿瘤-宿主反应，与多种肿瘤的预后相关，肿瘤前缘淋巴浸润密度与患者预后呈明显正相关。TILs会被肿瘤相关抗原和内源性释放的白细胞介素-2（IL-2）部分激活。本研究的目的是验证皮下注射IL-2是否能够增强胃癌患者的TILs，并影响患者的预后。
我们纳入了39例连续的胃腺癌患者。患者被随机分为单纯手术治疗组（对照组，20例患者）或手术加术前IL-2给药治疗组（治疗组，19例患者）。术前和术后评估总淋巴细胞、CD4和CD4/CD8。评估肿瘤组织学中的瘤周基质反应、中性粒细胞、淋巴细胞和嗜酸性粒细胞浸润情况，并比较两组的生存曲线。
IL-2治疗安全且耐受性良好，在IL-2治疗组中，术后第14天和第50天总淋巴细胞、CD4和CD4/CD8均较基线预处理值显著增加（p < 0.05）。两组间瘤周基质反应、中性粒细胞和嗜酸性粒细胞浸润无统计学差异。然而，我们观察到IL-2治疗患者与对照患者之间在瘤周和瘤内淋巴细胞浸润方面存在统计学显著差异（p = 0.000026）。IL-2组的中位总生存期和无病生存期比对照组更长，尽管不显著（分别为p = 0.089和p = 0.09）。
我们的数据表明，IL-2似乎能够诱导肿瘤炎症浸润发生实质性变化，改善宿主对肿瘤的活性，并增强胃癌患者的TILs现象。这一特征似乎改善了患者的预后。
