Mechanisms and characteristics of subcapsular sinus macrophages in tumor immunity: a narrative review

Background and Objective: Lymph nodes constitute an integral component of the secondary lymphoid organs, housing a diverse population of macrophages. Macrophages exhibit heterogeneity in terms of localization, phenotype and ontogeny. Recent evidence has established that subcapsular sinus macrophages (SCSMs) are the initial cells exposed to antigens from afferent lymph vessels, playing a crucial role in the host immune response against invading pathogens and tumor cells. In order to summarize the role and mechanisms of SCSM in tumor immunity, this study systematically reviews research on SCSMs in tumor immunity.Methods: A systematic search was conducted in PubMed and Web of Science to identify articles investigating clinical significance and mechanisms of SCSMs. Study eligibility was independently evaluated by two authors based on the assessment of titles, abstracts and full-texts.Key Content and Findings: The narrative review included a total of 17 studies. Previous research consistently showed that a high level of SCSM in patients with various carcinomas is associated with a favorable long-term prognosis. SCSM acts as the front-line defender in antitumor activity, engaging in intricate communication with other immune cells. Moreover, SCSM could directly and indirectly modulate tumor immunity, and the integrity of SCSM layer is interrupted in disease status. Several studies explored the feasibility of targeting SCSM to activate immunity against tumors. However, the direct molecular interactions and alternation in signal pathway in the tumor immunity of SCSM are less well established in previous researches.Conclusions: This narrative review underscores the critical role of SCSM in tumor immunity. Future studies should focus on the deeper mechanism underlying SCSMs and explore their clinical applications.