The intricate, lifelong conversation between blood vessels and immune system is fundamental to health, and its breakdown is pathogenic to many diseases. A review, published on February 10, 2026, in Immunity & Inflammation by Prof. Yihai Cao at the Karolinska Institute, Sweden, provides a systematic and mechanistic framework for understanding this dynamic crosstalk, offering a unified perspective on how vascular endothelial cells orchestrate immune responses and how their dysfunction leads to pathology.
The analysis begins by tracing the shared embryonic origin of blood vessel cells and immune cells from a common progenitor, the hemaniogioblast, establishing an intrinsic biological link. This foundational connection persists throughout adulthood, most notably within the bone marrow, where specialized endothelial cells form a regulatory niche, secreting factors like SDF-1 and expressing adhesion molecules, such as VCAM-1, to maintain hematopoietic stem cells and guide their differentiation, highlighting the vasculature's role as a cornerstone of the immune system's genesis and maintenance.
The review then discusses the coordinated process of immune cell trafficking, the process by which immune cells exit the bloodstream to enter tissues—a sequence known as the leukocyte recruitment cascade. The article compares the distinct molecular mechanisms employed by different immune cell subsets. For instance, it details how lymphocytes primarily utilize the integrin LFA-1 and chemokine receptors like CXCR4 for homing, while monocytes rely on VLA-4 and CCR2. This comparative analysis underscores the specificity with which endothelial cells, through displayed signals like selectins and chemokines, regulate the precise recruitment of immune cell populations to specific sites.
The article mainly focuses on reviewing the mechanisms of interaction between blood vessels and immune cells in regulating physiological process and pathological conditions across multiple organ systems. In physiological contexts like wound healing, the review describes the temporally coordinated partnership between controlled angiogenesis and acute inflammation to facilitate repair. This partnership becomes pathological in conditions like cancer. The article elaborates on how the abnormal, leaky vasculature of tumors creates a hypoxic and acidic microenvironment that directly inhibits cytotoxic T-cell function and promotes the recruitment of immunosuppressive cells, including regulatory T cells and myeloid-derived suppressor cells. This establishes a vicious cycle, where abnormal blood vessels foster an immune-cold tumor microenvironment, which in turn drives more aberrant vessel growth.
Beyond oncology, the review delves into cardiovascular and metabolic diseases. It explains how in atherosclerosis, pro-inflammatory activation of endothelial cells at sites of disturbed blood flow initiates plaque formation. The work cites specific mechanisms, such as the flow-induced expression of the membrane-bound chemokine CX3CL1 on endothelial surfaces, which captures circulating CX3CR1-expressing monocytes, anchoring them to the arterial wall. Similar dysfunctional crosstalk is highlighted in rheumatoid arthritis, where synovial vascular hyperplasia aggravates chronic joint inflammation, and in obesity, where expanded adipose tissue vasculature contributes to systemic metabolic inflammation and insulin resistance.
This review carries significant translational implications. It provides robust mechanistic evidence for combining anti-angiogenic therapies with immune checkpoint inhibitors in cancer therapy, pointing out both their synergistic potential and the heterogeneity of clinical responses. The concept of "vascular normalization"—therapeutically pruning and stabilizing tumor vessels to improve perfusion and reduce immunosuppression—is presented as a promising strategy to enhance immunotherapy efficacy. The author proposes that “ future interventions could target specific vascular-immune interaction hubs, such as tumor-associated high endothelial venules, which are specialized for lymphocyte entry. ”
Prof. Cao further emphasizes the integrative perspective: " Viewing the vasculature and immunity as a deeply interconnected functional unit is transformative. It reveals common pathogenic pathways across diverse diseases and uncovers novel nodes for therapeutic intervention that single-system approaches might miss. " The review concludes by advocating for the use of advanced spatial transcriptomics and single-cell technologies to map the heterogeneity of these interactions across tissues and disease stages, paving the way for the next generation of precise, mechanism-based therapies for those prevalent and challenging conditions.
About Immunity & Inflammation
Immunity & Inflammation is a newly launched open-access journal co-published by the Chinese Society for Immunology and Springer Nature under the leadership of Editors-in-Chief Prof. Xuetao Cao and Prof. Jules A. Hoffmann. Immunity & Inflammation aims to publish major scientific questions and cutting-edge advances that explore groundbreaking discoveries and insights across the spectrum of immunity and inflammation, from basic science to translational and clinical research.
Website: https://link.springer.com/journal/44466
About Author
Prof. Yihai Cao from the Karolinska Institute, Sweden
Prof. Cao is a Professor at the Karolinska Institute and a Foreign Member of the Chinese Academy of Engineering. He is a pioneering researcher in the field of angiogenesis, his work has fundamentally advanced the clinical application. He is a recipient of the Axel Hirsch Prize and the Tan Jiazhen Life Science International Cooperation Award. His research focuses on the mechanisms of angiogenesis in metabolic diseases, cancer, cardiovascular, and ophthalmological conditions.
Funding information
The author´s laboratory is supported through research grants from the Swedish Cancer Foundation, the Strategic Research Areas (SFO)–Stem Cell and Regenerative Medicine Foundation, the Karolinska Institute Foundation, the NOVO Nordisk Foundation, the Swedish Research Council (Project No. 2016-02215, Project No. 2019-01502, Project No. 2021-06122), the Swedish Research Council-the National Natural Science Foundation of China joint grants, the Hong Kong Centre for Cerebro-Cardiovascular Health Engineering; and the Horizon Europe grant-PERSEUS (Action Number: 101099423).
Systematic review
Not applicable
Mechanistic understanding of crosstalk between blood vessels and immunity and inflammation in diseases
10-Feb-2026
The corresponding author Yihai Cao is a member of the Editorial Board of the journal Immunity & Inflammation. However, he was not involved in the peer-review or decision-making process for this manuscript. The author declares no other competing interests.