Shibutani Masatsune, Maeda Kiyoshi, Nagahara Hisashi, Fukuoka Tatsunari, Iseki Yasuhito, Matsutani Shinji, Kashiwagi Shinichiro, Tanaka Hiroaki, Hirakawa Kosei, Ohira Masaichi
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
In Vivo. 2018 Jan-Feb;32(1):151-158. doi: 10.21873/invivo.11218.
BACKGROUND/AIM: The anticancer immune response has been reported to contribute to the success of chemotherapy. The aim of this study was to evaluate the significance of the measurement of tumor-infiltrating lymphocytes (TILs) in the primary tumor using the method proposed by the International TILs Working Group as a prognostic marker of chemotherapeutic outcomes in patients with stage IV colorectal cancer (CRC).
A total of 57 patients with stage IV CRC who underwent palliative chemotherapy after resection of the primary tumor were enrolled. Hematoxylin and eosin (H-E)-stained tumor sections were used for the evaluation of TILs. The density of TILs was assessed by measuring the area occupied by mononuclear inflammatory cells over the total stromal area at the invasive margin. Immunohistochemistry for CD8 was also performed, and the number of immunoreactive cytotoxic T-lymphocytes (CTLs) at the invasive margin was counted.
Thirty patients were classified into the high-TILs group, and 27 patients were classified into the low-TILs group. The high-TILs group had a significantly higher chemotherapeutic response rate (79.3% vs. 48.1%, p=0.025) and better progression-free survival (median survival time: 10.1 m vs. 7.3 m, p=0.0133) than the low-TILs group. Furthermore, the high-TILs group had a significantly better overall survival than the low-TILs group (median survival time: 35.5 m vs. 22.4 m, p=0.0221). The density of TILs evaluated using the H-E-stained sections showed a strong association with the number of CTLs (p<0.001).
The measurement of TILs in the primary tumor using the method proposed by the International TILs Working Group can be used as a prognostic marker of the clinical effectiveness of palliative chemotherapy in patients with stage IV CRC.
背景/目的:据报道,抗癌免疫反应有助于化疗取得成功。本研究旨在评估采用国际肿瘤浸润淋巴细胞(TILs)工作组提出的方法检测原发性肿瘤中TILs作为IV期结直肠癌(CRC)患者化疗预后标志物的意义。
共纳入57例IV期CRC患者,这些患者在原发性肿瘤切除后接受了姑息化疗。苏木精和伊红(H-E)染色的肿瘤切片用于评估TILs。通过测量浸润边缘处单核炎症细胞在总基质面积中所占的面积来评估TILs的密度。还进行了CD8免疫组织化学检测,并对浸润边缘处免疫反应性细胞毒性T淋巴细胞(CTLs)的数量进行计数。
30例患者被分类为高TILs组,27例患者被分类为低TILs组。高TILs组的化疗缓解率显著高于低TILs组(79.3%对48.1%,p=0.025),无进展生存期更好(中位生存期:10.1个月对7.3个月,p=0.0133)。此外,高TILs组的总生存期显著优于低TILs组(中位生存期:35.5个月对22.4个月,p=0.0221)。使用H-E染色切片评估的TILs密度与CTLs数量密切相关(p<0.001)。
采用国际TILs工作组提出的方法检测原发性肿瘤中的TILs可作为IV期CRC患者姑息化疗临床疗效的预后标志物。