血管内皮生长因子抑制剂通过肿瘤微环境免疫抑制促进晚期结直肠癌的抗肿瘤反应。
Vascular endothelial growth factor inhibitors promote antitumor responses via tumor microenvironment immunosuppression in advanced colorectal cancer.
发表日期:2023 Mar 29
作者:
Yuki Hamada, Kiyonori Tanoue, Yoshiaki Kita, Kan Tanabe, Kentaro Hokonohara, Masumi Wada, Yuto Hozaka, Hideyuki Oi, Chieri Nakayama, Michiyo Higashi, Takaaki Arigami, Shinichiro Mori, Takao Ohtsuka
来源:
Cellular & Molecular Immunology
摘要:
本研究旨在调查接受血管内皮生长因子(VEGF)抑制剂治疗晚期结直肠癌的患者肿瘤免疫环境的变化。纳入患有T3或T4结直肠癌的患者(n = 135)进行回顾性研究。他们被分为未接受术前治疗的患者(UPFRONT组,n = 54),接受FOLFOX作为术前化疗的患者(FOLFOX组,n = 55)和接受FOLFOX和贝伐单抗联合切除非手术切除的结直肠癌的患者(B-MAB组,n = 26)。在手术标本的癌细胞区(CC)和基质细胞区(ST)中,免疫组织化学评估了细胞毒性T淋巴细胞(CTL)的数量,FOXP3+淋巴细胞(包括调节T细胞(Tregs)),CD163+单核细胞(包括M2型肿瘤相关巨噬细胞(TAM-M2型))以及程序性细胞死亡1(PD-1)+淋巴细胞,并在三个组之间进行比较。在两个区域中,CTL的数量在三个组之间没有差异。在B-MAB组中,ST中的PD-1+细胞,两个区域中的FOXP3+淋巴细胞和ST中的CD163+单核细胞的数量比其他两个组要低,并观察到与组织学治疗效果的相关性。在晚期结直肠癌中,VEGF抑制剂可能会降低PD-1+细胞的数量,并抑制FOXP3+淋巴细胞和CD163+单核细胞进入肿瘤环境的浸润。
This study aims to investigate changes in the tumor immune environment of patients who underwent therapy with a vascular endothelial growth factor (VEGF) inhibitor for advanced colorectal cancer.Patients (n = 135) with T3 or T4 colorectal cancer were included in this retrospective study. They were classified as follows: patients who had not received preoperative treatment (UPFRONT group, n = 54), who had received FOLFOX as preoperative chemotherapy (FOLFOX group, n = 55), and who had undergone resection after combination FOLFOX and bevacizumab as unresectable colorectal cancer (B-MAB group, n = 26). The number of cytotoxic T lymphocytes (CTLs), FOXP3+ lymphocytes (including regulatory T cells (Tregs)), CD163+ monocytes (including M2-type tumor-associated macrophages (TAM-M2 type)), and programmed cell death 1 (PD-1)+ lymphocytes was evaluated immunohistochemically in the cancer cell area (CC) and stromal cell area (ST) of surgical specimens, and compared among the three groups.The CTL population did not differ among the three groups in both areas. In the B-MAB group, the numbers of PD-1+ cells in the ST, FOXP3+ lymphocytes in both areas, and CD163+monocytes in the ST was lower than that in the other two groups, and a correlation with the histological therapeutic effect was observed.In advanced colorectal cancer, VEGF inhibitors may decrease the number of PD-1+ cells and inhibit the infiltration of FOXP3+ lymphocytes and CD163+monocytes into the tumor environment.