抗 PD-1 抗体全身或腹腔给药治疗胃癌腹膜转移的效果。
Effect of Systemic or Intraperitoneal Administration of Anti-PD-1 Antibody for Peritoneal Metastases from Gastric Cancer.
机构信息
Department of Gastrointestinal Surgery, Jichi Medical University, Simotsuke, Japan.
Department of Gastrointestinal Surgery, Jichi Medical University, Simotsuke, Japan
出版信息
In Vivo. 2022 May-Jun;36(3):1126-1135. doi: 10.21873/invivo.12811.
BACKGROUND/AIM: Programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) blockade therapy is widely used for the treatment of patients with metastatic gastric cancer (GC). However, it is unclear how PD-1 antibodies affect the local immunity related to the growth of peritoneal metastases (PM). The clinical efficacy of PD-1/PD-L1 inhibitors against PM from GC has not been clearly determined.
MATERIALS AND METHODS
We established a highly metastatic subclone of murine GC cells to the peritoneum, YTN16P, by in vivo selection and evaluated the effects of intravenous (IV) or intraperitoneal (IP) administration of anti-PD-1 antibody on PM in immunocompetent mice model. Phenotypes of immune cells in the spleen and peritoneal metastatic lesions were determined with flow cytometry and immunohistochemistry.
RESULTS
IP inoculation of YTN16P (1×10) resulted in multiple mesenteric metastases after 3 weeks. IV and IP administration of anti-PD-1mAb reduced the number of metastases to the mesentery by 30~40% compared with isotype controls. However, no differences were observed depending on the route of administration. Although splenocyte phenotypes were not altered, the densities of CD8(+) T cells in peritoneal tumors were significantly increased, whereas those of Gr-1(+) myeloid derived suppressor cells (MDSC) were significantly reduced in mice treated with anti-PD-1 mAb.
CONCLUSION
PD-1 blockade therapy remodels the cellular immune composition of peritoneal tumors, which can partially suppress the PM from GC regardless of the route of administration. Adding anti-PD-1 antibody to chemotherapeutic regimens may enhance their anti-tumor effects against PM, which can lead to the prolongation of survival of patients with GC with peritoneal involvement.
背景/目的：程序性死亡受体-1（PD-1）/程序性死亡配体 1（PD-L1）阻断疗法被广泛用于治疗转移性胃癌（GC）患者。然而，PD-1 抗体如何影响与腹膜转移（PM）生长相关的局部免疫尚不清楚。PD-1/PD-L1 抑制剂对来自 GC 的 PM 的临床疗效尚未明确。
材料和方法
我们通过体内选择建立了一个高度转移性的鼠 GC 细胞亚系到腹膜，YTN16P，并在免疫功能正常的小鼠模型中评估了静脉（IV）或腹腔（IP）给予抗 PD-1 抗体对 PM 的影响。用流式细胞术和免疫组织化学法测定脾和腹膜转移性病变中免疫细胞的表型。
结果
IP 接种 YTN16P（1×10）在 3 周后导致多个肠系膜转移。与同型对照相比，IV 和 IP 给予抗 PD-1mAb 可使转移到肠系膜的数量减少 30~40%。然而，给药途径没有差异。虽然脾细胞表型没有改变，但腹膜肿瘤中 CD8(+)T 细胞的密度显著增加，而用抗 PD-1 mAb 治疗的小鼠中 Gr-1(+)髓源抑制细胞（MDSC）的密度显著降低。
结论
PD-1 阻断疗法重塑了腹膜肿瘤的细胞免疫组成，无论给药途径如何，都可以部分抑制来自 GC 的 PM。在化疗方案中加入抗 PD-1 抗体可能会增强其对 PM 的抗肿瘤作用，从而延长有腹膜受累的 GC 患者的生存时间。
Zotero 插件