Mechanisms of resistance to immune checkpoint inhibitors and solutions to the problem

Abstract. Immune checkpoint inhibitors (ICIs) have now become one of the major clinical treatments for tumors, which can inhibit the negative immunomodulation and thus enable the immune system to function to treat tumors. However, as with other treatments, patients develop clinical resistance to ICIs, which is an important cause of ICI treatment failure and tumor recurrence. The body acquires resistance to ICIs through pathways such as regulatory T cells (Treg) that increase the expression of other immune checkpoints to resist immunity, Wnt/-catenin that affect the secretion of IFN and IFN and thus suppress T-cell activation, and the NF-B pathway that induces B cells to arrest in the G2/M phase and thus inhibit the differentiation of B cells into germinal center B cells. Targeting Tregs at targets such as OX40, using the Wnt/-catenin inhibitor XAV-939, and combining ICIs with radiotherapy and chemotherapy can resolve the issue of resistance to ICIs. In this paper, we review the specific mechanisms by which ICIs develop resistance and possible future solutions, with the purpose of discovering ways to the efficiency of ICIs in addressing cancer and exploring new avenues for future cancer therapy. In the future era of individualized medicine, the application of precision medicine in the treatment of cancer with ICIs is equally worthy of consideration.