Polyglutamine protein in tumor cells sensitizes tumor cells to natural killer cell cytolysis

Lu, Zhen; Bi, Jiacheng; Sun, Yimo; Yang, Xiaolu; Wan, Xiaochun

doi:10.1016/j.molimm.2020.06.008

Cited by 2 publications

(1 citation statement)

References 17 publications

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“…Moreover, since TRIM30a induces proteotoxic stress in these tumour cells, and NK cells are highly effective in killing stressed tumour cells [7], this could explain some of the increased NK cytotoxicity against these tumour cells in an NK celldependent manner. Our findings are in line with previous studies that established increased NK cell-mediated cytolysis of stressed tumour cells [7,11,42].…”

Section: Discussionsupporting

confidence: 93%

Suppression of protein quality control system by TRIM30a sensitises tumour cells to NK cell‐mediated immune surveillance

Afolabi,

Bi,

Chen

et al. 2023

Immunology

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Tumorigenesis entails circumventing cell‐intrinsic regulatory mechanisms while avoiding extrinsic immune surveillance and other host defence systems. Nevertheless, how tumour cells' ability to eliminate misfolded proteins affects immune surveillance remains poorly understood. In this study, we find that overexpression of murine tripartite motif‐containing protein 30a (TRIM30a) sensitises tumour cells to natural killer (NK) cells‐mediated cytolysis. TRIM30a has no effect on tumour cell proliferation or apoptosis in vitro. However, TRIM30a‐overexpressing tumour cells grow substantially slower than control tumour cells in immune‐competent mice but not in NK cell‐depleted mice. [Correction added on 04 October 2023, after first online publication: ‘NK‐depleted’ has been changed to ‘NK cell‐depleted’ in the preceding sentence.] Mechanistically, TRIM30a overexpression impedes the clearance of misfolded proteins and increases the production of reactive oxygen species induced by proteotoxic stress, implying that TRIM30a impairs protein quality control (PQC) systems in tumour cells. Furthermore, TRIM30a reduces expression of genes encoding proteasome subunits and antioxidant proteins. Our study demonstrates that TRIM30a is a potential tumour suppressor and immune modulator that promotes tumour cytolysis by NK cells, and suggests that an enhanced PQC and antioxidant capacity is an integral part of the immune escape mechanism during tumorigenesis.

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