Ectonucleoside triphosphate diphosphohydrolase 6: A double-edged sword in cancer prognosis and therapy

Abstract

Malignant diseases in both children and adults are a worldwide public health priority with a high socioeconomic burden. Ectonucleoside triphosphate diphosphohydrolase 6 (ENTPD6) molecule exhibits divergent expression patterns across different cancers. Its increased expression in some tumors may allow them to escape anti-tumor immune responses, potentially by inducing an immunosuppressive tumor microenvironment and favoring a poorer prognosis. Conversely, in vivo, a mutated ENTPD6 gene may induce effective cytotoxic T cell responses, thereby reducing liver tumor size. Additionally, low expression of ENTPD6 has been related to chemotherapy resistance, whereas specific ENTPD6-derived neoepitopes may potentially enhance the efficacy of immunotherapy. This paper analyses the dual roles and clinical utility of ENTPD6 in cancer.

Keywords: Ectonucleoside triphosphate diphosphohydrolase 6; Cancer; Prognosis; Therapy; Antitumor immunity

Core Tip: Ectonucleoside triphosphate diphosphohydrolase 6 (ENTPD6) has dual effects on cancer development and progression, influencing immune surveillance and immune evasion through tumor microenvironment modulation. It serves as a promising novel molecular biomarker for prognosis and for predicting cancer therapy responses. Furthermore, ENTPD6-derived neopeptide vaccines, as well as adoptive T-cell transfer using T cells engineered with T-cell receptors targeting ENTPD6, may constitute promising strategies in cancer immunotherapy.