Oncolytic vaccinia virus reinvigorates peritoneal immunity and cooperates with immune checkpoint inhibitor to suppress peritoneal carcinomatosis in colon cancer.

Journal for Immunotherapy of Cancer
Yu Seong LeeChan Kim

Abstract

Peritoneal carcinomatosis (PC) is a common and devastating manifestation of colon cancer and refractory to conventional anticancer therapeutics. During the peritoneal dissemination of colon cancer, peritoneal immunity is nullified by various mechanisms of immune evasion. Here, we employed the armed oncolytic vaccinia virus mJX-594 (JX) to rejuvenate the peritoneal antitumor immune responses in the treatment of PC. PC model of MC38 colon cancer was generated and intraperitoneally treated with JX and/or anti-programmed cell death protein 1 (PD-1) antibody. The peritoneal tumor burden, vascular leakage, and malignant ascites formation were then assessed. Tumors and peritoneal lavage cells were analyzed by flow cytometry, multiplex tissue imaging, and a NanoString assay. JX treatment effectively suppressed peritoneal cancer progression and malignant ascites formation. It also restored the peritoneal anticancer immunity by activating peritoneal dendritic cells (DCs) and CD8+ T cells. Moreover, JX selectively infected and killed peritoneal colon cancer cells and promoted the intratumoral infiltration of DCs and CD8+ T cells into peritoneal tumor nodules. JX reinvigorates anticancer immunity by reprogramming immune-related transcripti...Continue Reading

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Citations

Mar 7, 2021·Cancers·Ángela BellaFernando Aranda
Aug 8, 2021·International Journal of Molecular Sciences·Chang-Gon KimHong-Jae Chon

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
lavage
flow cytometry
FACS
PMA
ELISA
fluorescence-activated cell-sorting

Software Mentioned

FlowJo
GraphPad Prism
GSEA
GraphPad
ImageJ
PASW statistics

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