Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
Project for Immunogenomics, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Anticancer Res. 2023 Feb;43(2):613-620. doi: 10.21873/anticanres.16197.
BACKGROUND/AIM: Chemotherapy combined with anti-EGFR or anti-VEGF monoclonal antibodies (mAb) is widely used to treat patients with metastatic colorectal cancer (mCRC). Here, we investigated the effects of these antibodies on T-cell infiltration and T-cell receptor (TCR) repertoire variation in CRC liver metastases.
Ten patients with mCRC received chemotherapy in combination with anti-EGFR (n=6) or anti-VEGF (n=4) mAb. T-cell infiltration was examined for CD3 and CD8 by carrying out immunohistochemistry on biopsy or surgical specimens from liver metastases before and after treatment. TCR repertoire analysis was carried out on specimens with post-treatment CD3 T-cell infiltration.
T-cell infiltrations were approximately 83% (5/6) and 50% (2/4), following treatment with anti-EGFR or anti-VEGF mAb, respectively. TCR repertoire analysis revealed higher clonality and lower diversity of TCR alpha and beta (TRA and TRB) in the anti-VEGF mAb group than that in the anti-EGFR group mAb. Furthermore, the percentage of the common TCR clones between infiltrating T cells and T cells in peripheral blood was significantly lower in the anti-VEGF mAb group compared to that in the anti-EGFR mAb group.
The population of T cells infiltrating liver metastases in the anti-VEGF mAb group differed from that in the anti-EGFR mAb group.
背景/目的：化疗联合抗 EGFR 或抗 VEGF 单克隆抗体（mAb）广泛用于治疗转移性结直肠癌（mCRC）患者。在这里，我们研究了这些抗体对 CRC 肝转移中 T 细胞浸润和 T 细胞受体（TCR） repertoire 变化的影响。
10 名 mCRC 患者接受化疗联合抗 EGFR（n=6）或抗 VEGF（n=4）mAb 治疗。通过对治疗前后肝转移活检或手术标本进行 CD3 和 CD8 的免疫组织化学染色，检测 T 细胞浸润。对治疗后 CD3 T 细胞浸润的标本进行 TCR repertoire 分析。
抗 EGFR 和抗 VEGF mAb 治疗后，T 细胞浸润率分别约为 83%（5/6）和 50%（2/4）。TCR repertoire 分析显示，抗 VEGF mAb 组的 TRA 和 TRB 的克隆性更高，多样性更低。此外，与抗 EGFR mAb 组相比，抗 VEGF mAb 组浸润 T 细胞与外周血 T 细胞之间的共同 TCR 克隆百分比明显更低。
抗 VEGF mAb 组肝转移中浸润 T 细胞的群体与抗 EGFR mAb 组不同。
