<b>Background/Objectives:</b> Sirtuin 7 (SIRT7), a nuclear NAD<sup>+</sup>-dependent deacylase, plays multifaceted and sometimes opposing roles in tumorigenesis. By preserving chromatin architecture and genome integrity, SIRT7 protects against malignant transformation; however, once cancer is established, it can either sustain or restrain tumor growth through context-dependent signaling programs, albeit via largely unknown mechanisms. Recent findings have uncovered an additional-and previously underappreciated-dimension: SIRT7's capacity to modulate anti-cancer immunity. This review revisits the current understanding of SIRT7 in cancer by emphasizing its emerging immunomodulatory functions and influence on the tumor microenvironment. <b>Methods:</b> We conducted a comprehensive literature review up to October 2025 using the PubMed database to identify both tumor-intrinsic and tumor-extrinsic mechanisms linking SIRT7 to anti-cancer immunity and to relate the established molecular functions of SIRT7-such as its roles in metabolism, genome maintenance, and inflammatory regulation-to immune regulation. <b>Results:</b> SIRT7 directly regulates immune checkpoint expression and T cell metabolic fitness, thereby positioning it as a key node connecting tumor-intrinsic programs with immune surveillance. Moreover, by controlling molecular pathways such as metabolism, genomic stability, and inflammatory responses-both within cancer cells and across other components of the tumor microenvironment-SIRT7 may more broadly influence the immune landscape, orchestrating immune evasion or recognition. <b>Conclusions:</b> Deciphering how SIRT7's tumor-intrinsic and immunomodulatory functions intersect is essential for anticipating the consequences of its pharmacological targeting in cancer. A deeper understanding of this interplay will enable the rational design of combination strategies that integrate SIRT7 modulation with immunotherapy within a precision medicine framework.
Authors: Shahriar Tarighi, Zifan Ning, Andrés Gámez-García, Alejandro Vaquero, Thomas Braun, Alessandro Ianni
DOI: https://doi.org/10.3390/ph18121878
Publish Year: 2025
