Effect of Systemic or Intraperitoneal Administration of Anti-PD-1 Antibody for Peritoneal Metastases from Gastric Cancer.

Autor:	Kumagai Y; Department of Gastrointestinal Surgery, Jichi Medical University, Simotsuke, Japan., Futoh Y; Department of Gastrointestinal Surgery, Jichi Medical University, Simotsuke, Japan., Miyato H; Department of Gastrointestinal Surgery, Jichi Medical University, Simotsuke, Japan., Ohzawa H; Department of Gastrointestinal Surgery, Jichi Medical University, Simotsuke, Japan., Yamaguchi H; Department of Gastrointestinal Surgery, Jichi Medical University, Simotsuke, Japan., Saito S; Department of Gastrointestinal Surgery, Jichi Medical University, Simotsuke, Japan., Kurashina K; Department of Gastrointestinal Surgery, Jichi Medical University, Simotsuke, Japan., Hosoya Y; Department of Gastrointestinal Surgery, Jichi Medical University, Simotsuke, Japan., Lefor AK; Department of Gastrointestinal Surgery, Jichi Medical University, Simotsuke, Japan., Sata N; Department of Gastrointestinal Surgery, Jichi Medical University, Simotsuke, Japan., Kitayama J; Department of Gastrointestinal Surgery, Jichi Medical University, Simotsuke, Japan kitayama@jichi.ac.jp.
Jazyk:	angličtina
Zdroj:	In vivo (Athens, Greece) [In Vivo] 2022 May-Jun; Vol. 36 (3), pp. 1126-1135.
DOI:	10.21873/invivo.12811
Abstrakt:	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 6 ) 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. (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
Databáze:	MEDLINE
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