Besides, some of the immune-related factors associated with tumor invasion and metastasis such as HMGB1 and Toll-like receptor 4 (TLR4) play a considerable role in rebuilding TIM and promoting the development of pyroptosis that could also be upregulated by hypoxia (Liu et al., 2015; Wu et al., 2018; Tan et al., 2020; Zha et al., 2020; Yuan et al., 2021). This evidence concerns the gene HMGB1 and neoplasm.