Sadahiro Sotaro, Suzuki Toshiyuki, Tanaka Akira, Okada Kazutake, Saito Gota, Miyakita Hiroshi, Chan Lin Fung, Kamei Yutaro, Kajiwara Hiroshi, Nagase Hideki
Department of Surgery, Tokai University School of Medicine, Isehara, Japan
Department of Surgery, Tokai University School of Medicine, Isehara, Japan.
Anticancer Res. 2019 Apr;39(4):1997-2005. doi: 10.21873/anticanres.13310.
BACKGROUND/AIM: Immune checkpoint inhibitors are mainly used for right-sided, microsatellite instability-high colorectal tumors. In this study, the effects of oral uracil-tegafur plus leucovorin (UFT/LV) chemotherapy on the gene expressions of four immunotherapy targets and the amounts of tumor-infiltrating lymphocytes (TILs) were investigated.
Data of 260 patients with stage II or stage III colorectal cancer were analyzed. Gene expression and amount of TILs were evaluated using real-time reverse transcription polymerase chain reaction (CRT-PCR) assay and immunohistochemical staining, respectively.
Expression of CTLA4 and LAG3 in tumor tissues was significantly increased after UFT/LV chemotherapy, but only in left-sided tumors. The percentage of high-TIL, high-CD3 and high-FoxP3 patients in the UFT/LV group was significantly higher than that in the control group, only in left-sided tumors.
The increase in TILs count, especially of CD3+ T cells and FoxP3+ regulatory T cells, after UFT/LV chemotherapy were specific to left-sided colorectal cancers.
背景/目的：免疫检查点抑制剂主要用于右侧、微卫星高度不稳定的结直肠癌肿瘤。在本研究中，研究了口服尿嘧啶替加氟联合亚叶酸钙（UFT/LV）化疗对四个免疫治疗靶点的基因表达及肿瘤浸润淋巴细胞（TILs）数量的影响。
分析了260例II期或III期结直肠癌患者的数据。分别使用实时逆转录聚合酶链反应（CRT-PCR）检测和免疫组织化学染色评估TILs的基因表达和数量。
UFT/LV化疗后，肿瘤组织中CTLA4和LAG3的表达显著增加，但仅在左侧肿瘤中出现。UFT/LV组中高TIL、高CD3和高FoxP3患者的百分比显著高于对照组，同样仅在左侧肿瘤中出现。
UFT/LV化疗后TILs数量增加，尤其是CD3 + T细胞和FoxP3 + 调节性T细胞数量增加，这在左侧结直肠癌中具有特异性。
