DNA damage occurs throughout tumorigenesis and development. The immunogenicity of DNA makes it an immune stimulatory molecule that initiates strong inflammatory responses. The cGAS/STING pathway has been investigated as a critical receptor in both exogenous and endogenous DNA sensing to activate the innate immune response. Growing lines of evidence have indicated that activation of the cGAS/STING pathway is critical in antitumor immunity. Recent studies have demonstrated the outstanding advancement of this pathway in tumor-combined immunotherapy; accordingly, increased studies focus on exploration of STING pathway agonists and analogues. However, current studies propose the potential use of the cGAS/STING pathway in tumor initiation and metastasis. Here, we review the molecular mechanisms and activation of the cGAS/STING pathway, and the relationship between DNA damage and this pathway, particularly highlighting the remodeling of immune contexture in tumor environment (TME) triggered by cascade inflammatory signals. A detailed understanding of TME reprogramming initiated by this pathway may pave the way for the development of new therapeutic strategies and rational clinical application.

DNA is highly vulnerable to spontaneous and environmental timely damage in living cells. DNA damage may cause genetic instability and increase cancer risk if the damages are not repaired timely and efficiently. Human cells possess several DNA damage response (DDR) mechanisms to protect the integrity of their genome. Clarification of the mechanisms underlying the DNA damage response following lethal damage will facilitate the identification of therapeutic targets for cancers. Histone post-translational modifications (PTMs) have been indicated to play different roles in the repair of DNA damage. In this context, histone PTMs regulate recruitment of downstream effectors, and facilitate appropriate repair response. This review outlines the current understanding of different histone PTMs in response to DNA damage repair, besides, enumerates the role of new type PTMs such as histone succinylation and crotonylation in regulating DNA damage repair processes.

Cervical cancer represents a significant global health challenge, with complex cellular and molecular mechanisms driving its progression from HPV infection to invasive malignancy. This study employed an integrated approach combining single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (stRNA-seq) to comprehensively characterize the tumor microenvironment (TME) across different stages of cervical cancer development. Through analysis of samples from normal cervix, HPV-infected normal cervix, high-grade squamous intraepithelial lesions (HSIL), and invasive cervical cancer, we identified distinct cellular populations and their dynamic changes during disease progression. Our findings revealed significant heterogeneity in immune cell populations, particularly highlighting the role of SPP1+ macrophages that were substantially enriched in cervical cancer compared to precancerous and normal tissues. Cell-cell communication networks and spatial mapping demonstrated that SPP1+ macrophages interact extensively with immune cells through the SPP1-CD44 signaling axis. This interaction contributes to an immunosuppressive microenvironment through modulation of T cell function and promotion of tumor cell survival. Furthermore, high expression of SPP1 correlated with advanced tumor stages and poor overall survival in cervical cancer patients, highlighting its potential as a prognostic biomarker. Our comprehensive characterization of the cellular landscape and intercellular communication networks in cervical cancer progression provides valuable insights for the development of targeted therapeutic strategies aimed at modulating the TME, particularly through disruption of the SPP1-CD44 axis. These findings establish a foundation for more effective personalized approaches to improve clinical outcomes in cervical cancer patients.