Heterogeneity of myeloid cells in common cancers: Single cell insights and targeting strategies.

Tumor microenvironment (TME), is characterized by a complex and heterogenous composition involving a substantial population of immune cells. Myeloid cells comprising over half of the solid tumor mass, are undoubtedly one of the most prominent cell populations associated with tumors. Studies have unambiguously established that myeloid cells play a key role in tumor development, including immune suppression, pro-inflammation, promote tumor metastasis and angiogenesis, for example, tumor-associated macrophages promote tumor progression in a variety of common tumors, including lung cancer, through direct or indirect interactions with the TME. However, due to previous technological constraints, research on myeloid cells often tended to be conducted as studies with low throughput and limited resolution. For example, the conventional categorization of macrophages into M1-like and M2-like subsets based solely on their anti-tumor and pro-tumor roles has disregarded their continuum of states, resulting in an inadequate analysis of the high heterogeneity characterizing myeloid cells. The widespread adoption of single-cell RNA sequencing (scRNA-seq) in tumor immunology has propelled researchers into a new realm of understanding, leading to the establishment of novel subsets and targets. In this review, the origin of myeloid cells in high-incidence cancers, the functions of myeloid cell subsets examined through traditional and single-cell perspectives, as well as specific targeting strategies, are comprehensively outlined. As a result of this endeavor, we will gain a better understanding of myeloid cell heterogeneity, as well as contribute to the development of new therapeutic approaches.

Epigenetic regulation of pyroptosis in cancer: Molecular pathogenesis and targeting strategies.

Immune checkpoint blockade therapy has revolutionized the field of cancer treatment, leading to durable responses in patients with advanced and metastatic cancers where conventional therapies were insufficient. However, factors like immunosuppressive cells and immune checkpoint molecules within the tumor microenvironment (TME) can suppress the immune system and thus negatively affect the efficiency of immune checkpoint inhibitors. Pyroptosis, a gasdermin-induced programmed cell death, could transform "cold tumors" to "hot tumors" to improve the milieu of TME, thus enhancing the immune response and preventing tumor growth. Recently, evidence showed that epigenetics could regulate pyroptosis, which further affects tumorigenesis, suggesting that epigenetics-based tumor cells pyroptosis could be a promising therapeutic strategy. Hence, this review focuses on the pyroptotic mechanism and summarizes three common types of epigenetics, DNA methylation, histone modification, and non-coding RNA, all of which have a role in regulating the expression of transcription factors and proteins involved in pyroptosis in cancer. Especially, we discuss targeting strategies on epigenetic-regulated pyroptosis and provide insights on the future trend of cancer research which may fuel cancer therapies into a new step.