NK cells can potentiate anti–tumour responses

Prama Ghosh, Amity University Kolkata

Past proof in mice has exhibited that NK cell-inferred IFN-gamma can advance immunoevasion by chiselling the immunogenicity of creating tumours in a process known as cancer immunoediting. This process includes the disposal of the high immunogenic unedited tumour, followed by the inevitable break of less immunogenic altered tumour cell variants that can get away from recognition or elimination by the immune system.

Cancer immunosurveillance is a process in which natural killer (NK) cells, innate lymphocytes which patrol host tissues against transformed cells. According to research, fibrosarcomas edited by NK cells- decrease the expression of 17 conserved IFN-gamma-inducible genes as compared to unedited tumour cells. Three genes, namely, Psmb8, Trim21, Parp12, have been identified whose high-expression in tumour samples enhances the survival of patients with breast cancer, melanoma, and sarcoma.

While NK cell-altered fibrosarcomas showed protection from IFN-gamma-mediated development suspension in vitro, functional knockouts of individual interferon-stimulated genes (ISGs) were not needed for the outgrowth of unedited tumour cell lines in vitro and in vivo contrasted with complete loss of IFN signalling. Moreover, knockout of IFN-gamma-intrinsic signalling using erasure of Ifngr in altered B16 F10 and E0771 LMB metastatic cancer cell lines did not affect the survival of the host following lung metastasis. 

Together, these outcomes recommend that unedited tumours can be chosen for decreased IFN-gamma signalling to sidestep immune responses in vivo and, as a result, tumour-extrinsic IFN signalling might be more significant for potentiating durable anti-tumour responses to solid tumours.

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Reference: NK cells promote cancer immunoediting through tumour-intrinsic loss of interferon-stimulated gene expression, Yung Yu Wong, Luke Riggan, Christopher Huerta, Matthew Moldenhauer, Edgar Perez Reyes, Timothy E O’Sullivan, bioRxiv 2020.11.23.394353; 

doi: https://doi.org/10.1101/2020.11.23.394353

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