NLRs in tumor chemotherapy resistance: A double-edged sword

Abstract

Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are a numerous family of cytoplasmic proteins. Members of this family not only function as innate immune sensors, but also serve as transcriptional regulators of major histocompatibility complex class II (MHC II) and major histocompatibility complex class I (MHC I) genes to activate adaptive immunity. Furthermore, NLRs are involved in mediating various signaling pathways, including the inflammasome. To date, extensive research has been conducted on the contradictory roles and mechanisms of NLRs in the occurrence, development, invasion, and metastasis of tumors within the tumor microenvironment (TME). The double-edged sword effect (either positive or negative role) of NLRs in the treatment of malignant tumors has attracted increasing attention in recent years, making these a promising bidirectional therapeutic target for such tumors. Rational utilization of the double-edged sword nature of NLRs can provide a feasible solution for improving the efficacy of malignant tumor treatment and overcoming chemotherapy resistance. This article provides a systematic review of the influence of the NLR family on chemosensitivity in different malignant tumors and the regulatory mechanisms of their upstream and downstream signaling pathways. In doing do, we aim to elucidate the dual role of NLRs in promoting and combating tumor chemotherapy resistance, and elucidate their application value in tumor chemotherapy resistance.