Background <p>Although the crosstalk between the immune system and tumour endothelial cells has been extensively investigated, interactions with tumour-associated pericytes (TAPs) remain poorly understood. Such issue may be of great interest considering the immunoregulatory roles of pericytes reported in both healthy and tumour tissues. This systematic review integrates current evidence on TAP–immune system interplay, encompassing functional roles, molecular mechanisms, associated biomarkers, and in vitro assessment methodologies. Preclinical investigations on the anticancer potential of TAP-targeted immunotherapies were also critically analysed, complemented by a meta-analysis assessing TAP-mediated immune regulation across distinct malignancies with a larger sample size.</p> Methods <p>Following the 2020 PRISMA guidelines, literature searches were conducted in PubMed, Web of Science, and Scopus for studies published up to February 2026. Of 3,557 records, 64 met the inclusion criteria after multi-stage screening (“title and abstract,” “full text” and “reference check”). Risk of bias was assessed using the OHAT tool for in vitro studies and the SYRCLE tool for in vivo research. Meta-analyses were performed using UALCAN and TIMER platforms.</p> Results <p>Our findings identified tumour-associated macrophages (TAMs) as the main immune regulators of TAPs, while TAPs modulate a broad range of immune cells—including TAMs, dendritic cells, B and T lymphocytes, regulatory T cells, myeloid-derived suppressor cells, and natural killer cells—thereby promoting an immunosuppressive tumour microenvironment. Indeed, experimental studies demonstrate the capacity of TAPs to reduce the anti-tumour efficacy of traditional cancer immunotherapies like inhibitory immune checkpoint blockade or adoptive immune cells therapies. Evidence remains scarce for certain cancers (e.g., cholangiocarcinoma, hepatic, and head and neck squamous cell carcinoma) and for lymphatic TAPs. Marked heterogeneity among TAPs and the limited availability of commercial pericyte-like cell lines represent major experimental challenges. Immunotherapies targeting TAPs, such as cancer vaccines and CAR-engineered immune cells, showed promising preclinical efficacy, highlighting their potential as translational medicine. Our meta-analysis further supports the strong immunosuppressive potential of TAPs, even in the underexplored malignancies above mentioned.</p> Conclusions <p>Collectively, this study highlights the crucial interplay between TAPs and immune cells in tumour biology and underscores the therapeutic promise of TAP-targeted immunotherapies, along with the importance of long-term evaluation of TAP-targeted immunotherapies and the development of standardized pericyte-like cell models.</p> Trial registration <p>The section “Immunotherapies Targeting TAPs” was registered in PROSPERO (ID: CRD420251053567).</p>