Interplay between ISG15/ISGylation and cancer therapy

Therapy typeCancer cellsThe described role of ISG15 in cancer therapyReference
ChemotherapyA549 lung cancer cells

Resistance to cisplatin is observed due to the silencing of ISG15

The reparation of cisplatin-damaged DNA in A549 cells reduces ISG15 expression

Chemotherapy and targeted therapyOvarian cancer cellsWild-type ISG15 overexpression (but not mutant ISG15 that is incapable of ISGylation) decreases ABCC2 protein levels, sensitizing resistant ovarian cancer cells to cisplatin[110]
SFTThe expression of CSC-related genes is decreased by ISG15 downregulation, resulting in increased cell death in 3D cultures after doxorubicin, pazopanib, or trabectedin treatment[111]
Chemotherapy and radiationNPC cellsIn vivo tumorigenicity and resistance to radiation and DDP by ISG15 overexpression[74]
RadiotherapyChronic myeloid leukemia and colorectal carcinoma Cytokines and antigen presentation-associated proteins can be the target of ISGylation. Hence, the downregulation of USP18 enhances the response of CTLs, and cancer cells can become more susceptible to radiotherapy[112]
ImmunotherapyCRCLm-LLO-ISG15 in an immunocompetent CRC murine model generates an anti-tumor response[107]
RCCLm-LLO-ISG15 vaccine in subcutaneous and orthotopic RCC mouse models results in adequate CTL-based immunotherapy, generating anti-tumor activity.[108]
Other therapiesCervical cancer, leukemia, and myeloma

The loss of NF-κB signaling causes ISG15 expression-induced apoptosis

Clioquinol and mefloquine treatments induce high levels of ISG15


SFT: solitary fibrous tumor; ABCC2: ATP binding cassette subfamily C member 2; 3D: three dimensions; NPC: nasopharyngeal carcinoma; DDP: cisplatin; RCC: Renal cell carcinoma; CTLs: cytotoxic T lymphocytes; NF-κB: nuclear factor-κB