A Double-Edged Role for SIRT7 in Cancer: Can Anti-Cancer Immunity Tip the Balance?

Background/Objectives: Sirtuin 7 (SIRT7), a nuclear NAD+-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. Methods: 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. Results: 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. Conclusions: 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.