TGF beta secreted by B16 melanoma antagonizes cancer gene immunotherapy bystander effect

Cancer Immunology, Immunotherapy : CII
Claudia Penafuerte, Jacques Galipeau

Abstract

Tumor-targeted delivery of immune stimulatory genes, such as pro-inflammatory cytokines and suicide genes, has shown to cure mouse models of cancer. Total tumor eradication was also found to occur despite subtotal tumor engineering; a phenomenon coined the "bystander effect". The bystander effect in immune competent animals arises mostly from recruitment of a cancer lytic cell-mediated immune response to local and distant tumor cells which escaped gene modification. We have previously described a Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Interleukin 2 (IL2) fusokine (aka GIFT2) which serves as a potent anticancer cytokine and it here served as a means to understand the mechanistic underpinnings to the immune bystander effect in an immune competent model of B16 melanoma. As expected, we observed that GIFT2 secreted by genetically engineered B16 tumor cells induces a bystander effect on non modified B16 cells, when admixed in a 1:1 ratio. However, despite keeping the 1:1 ratio constant, the immune bystander effect was completely lost as the total B16 cell number was increased from 10(4) to 10(6) which correlated with a sharp reduction in the number of tumor-infiltrating NK cells. We found that B16 secrete biol...Continue Reading

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Citations

Sep 29, 2011·Molecular Cancer·Moutih RafeiJacques Galipeau
Mar 28, 2013·Clinical & Developmental Immunology·Pablo A GonzálezAlexis M Kalergis
Oct 28, 2014·The Journal of Clinical Investigation·Regina LinQi-Jing Li
May 7, 2014·Oncoimmunology·Valérie Janelle, Alain Lamarre
May 10, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Claudia PenafuerteJacques Galipeau
Feb 13, 2018·Oncology Letters·Xiao-Ling FengLing Hu
Jul 9, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maite AlvarezWilliam J Murphy
Dec 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Andrey V MarkovMarina A Zenkova
Apr 4, 2021·Cancers·Hansol LeeJames S Wilmott

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