A gastric cancer cell derived extracellular compounds suppresses CD161+CD3- lymphocytes and aggravates tumor formation in a syngeneic mouse model. (April 2020)

• Record Type: Journal Article
• Authors: Adithan, Aravinthan; John Peter, Judith Sharmila; Mohammad, Amjad Hossain; Kim, Bumseok; Kang, Chang-Won; Kim, Nam Soo; Hwang, Ki-Chul; Kim, Jong-Hoon
• Is Part Of: Molecular immunology. Volume 120(2020:Apr.)
• Page Start: 136
• Page End: 145
• Publication Date: 2020-04
• Subjects: Gastric cancer cell -- Cytolytic activity -- Natural killer cells -- Cytokines -- Tumor expansion -- Syngeneic mouse; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2020.02.016
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: This study identified several cytokines/chemokines in the human gastric cancer cell derived extra cellular compound (GC-EC). The GC-EC selectively suppresses NK cell population in splenocytes. The aggravation of tumor formation was prominent in the presence of GC-EC in syngeneic mouse model. Abstract: Evasion of the immune system is often associated with malignant tumors. The cancer cell microenvironment plays an important role in tumor progression, but its mechanism is largely unknown. Here we show that an extracellular compound derived from gastric cancer (GC-EC) selectively suppresses CD161 + CD3 − natural killer (NK) cells. Splenocytes treated with GC-EC showed considerable proliferation and the CD161 + CD3 − NK cell population was time-dependently suppressed. Intracellular staining of IFN-γ was shown to be down-regulated in concert with granzyme B and perforin. A cytotoxicity assay of splenocytes treated with GC-EC against K-562 cells showed a significant reduction in cytolytic activity. Further, the immune-suppressive effect of GC-EC was more evident in a syngeneic tumor model in C57BL/6 mice. Animals treated with B16 F10 and GC-EC exhibited more aggravated tumor formation than animals treated with B16 F10 only. We demonstrated that inhibition of apoptosis while increasing PI3 K/AKT levels may provoke tumor formation by GC-EC. A cytokine array revealed the presence of several cytokines in GC-EC that negatively regulate immune cytolytic activity and could be potential candidates for immune-suppressive effects.