Takemoto Nobuyuki, Konishi Fumio, Yamashita Keisuke, Kojima Masayuki, Furukawa Taiji, Miyakura Yasuyuki, Shitoh Kazuhisa, Nagai Hideo
Department of Surgery, Omiya Medical Center, Jichi Medical School, Saitama, Japan.
Jpn J Clin Oncol. 2004 Feb;34(2):90-8. doi: 10.1093/jjco/hyh018.
Tumor-infiltrating lymphocytes (TIL) are strictly divided into two categories: those lymphocytes in stroma and those in between cancer cells. However, there has been no fully adequate comparison of these two categories, especially analysis in relation to microsatellite instability (MSI).
The materials were derived from patients with colorectal cancer who underwent surgery in Jichi Medical School and Omiya Medical Center. There were 19 hereditary non-polyposis colorectal cancer (HNPCC) patients who were compatible with Japanese criteria A and 106 patients with sporadic colorectal cancer (sCRC) in either Dukes B or C stage. As microsatellite markers, the global standard five markers were selected. Immunohistochemical analysis was performed using the anti-CD3, -CD4, -CD8 and -S-100 antibodies and the results were evaluated according to the degree of infiltration, which was classified into three grades.
As for stroma-infiltrating lymphocytes (SIL) in sCRCs, severe infiltration was observed in 20% of high microsatellite instability (MSI-H) patients and 12.8% of low microsatellite instability (MSI-L)/stable microsatellite (MSS) patients without a statistically significant difference. In contrast, severe infiltration of intra-tumor cell-infiltrating lymphocytes (ITCIL) was observed in 41.7% of MSI-H sCRC patients and 4.3% of MSI-L/MSS patients. Thus, there was a close correlation between ITCIL severity and increased microsatellite instability (P < 0.001). In examination of ITCIL, patients with severe infiltration tended to show a better survival rate than those with moderate or mild infiltration.
The present study suggests that different factors are involved in the infiltration of SIL and ITCIL. Although there were no statistically significant differences, the cumulative survival rates tended to be higher in severe ITCIL cases than in those with moderate and poor ITCIL (P < 0.09). We suggest that there might be a possibility of ITCIL having a role for a better prognosis after colorectal cancer surgery, which is closely related to MSI.
肿瘤浸润淋巴细胞（TIL）严格分为两类：基质中的淋巴细胞和癌细胞之间的淋巴细胞。然而，这两类淋巴细胞尚未得到充分的比较，尤其是与微卫星不稳定性（MSI）相关的分析。
材料来自于在秩父市立医科大学和大宫医疗中心接受手术的结直肠癌患者。有19例符合日本标准A的遗传性非息肉病性结直肠癌（HNPCC）患者和106例处于Dukes B或C期的散发性结直肠癌（sCRC）患者。作为微卫星标记，选择了全球标准的五个标记。使用抗CD3、抗CD4、抗CD8和抗S-100抗体进行免疫组织化学分析，并根据浸润程度对结果进行评估，浸润程度分为三个等级。
对于sCRC中的基质浸润淋巴细胞（SIL），在20%的高微卫星不稳定性（MSI-H）患者和12.8%的低微卫星不稳定性（MSI-L）/稳定微卫星（MSS）患者中观察到严重浸润，差异无统计学意义。相比之下，在41.7%的MSI-H sCRC患者和4.3%的MSI-L/MSS患者中观察到肿瘤内细胞浸润淋巴细胞（ITCIL）的严重浸润。因此，ITCIL严重程度与微卫星不稳定性增加密切相关（P < 0.001）。在ITCIL检查中，严重浸润的患者往往比中度或轻度浸润的患者生存率更高。
本研究表明，SIL和ITCIL的浸润涉及不同因素。虽然差异无统计学意义，但严重ITCIL病例的累积生存率往往高于中度和差的ITCIL病例（P < 0.09）。我们认为，ITCIL可能对结直肠癌手术后的更好预后具有作用，这与MSI密切相关。
