The dual role of HMGB1 in Cancer Immunity and its potential in immunotherapy

As we commemorate World Cancer Day, it’s crucial to spotlight groundbreaking researches that drive our path to discovery cancer mechanism.
Among these researches, High Mobility Group Box 1 (HMGB1) and its dual role in tumor immunity has emerged as a pivotal player in the complex interplay of tumor immunity, demonstrating a dual role in understanding its potential as target in cancer immunotherapy.

HMGB1, a non-histone protein highly present in mammalian cell nuclei, emerges in fact as both a foe and ally within the cancer battlefield, underlineing one more time the complexity of our immune system’s interaction with cancer.

Immunosuppressive Effects: High Mobility Group Box 1 intricately modulates the tumor microenvironment by fostering the proliferation and survival of myeloid-derived suppressor cells (MDSCs), aiding in the differentiation and activation of regulatory T cells (Tregs), and promoting the recruitment and polarization of tumor-associated macrophages (TAMs). These actions contribute to tumor immune escape and suppression of antitumor immunity.

Immunoenhancing Effects: conversely, HMGB1 is instrumental in orchestrating immunogenic cell death (ICD), a critical mechanism in anticancer therapies. Through its release during cell death, HMGB1 signals danger to the immune system, helping the activation and recruitment of antigen-presenting cells and thereby enhancing the cytotoxic T lymphocyte response against tumor cells.

Understanding the real mechanisms of HMGB1 action, including its secretion pathways, the impact of post-translational modifications, and its interaction with cellular receptors, is paramount. Addressing these aspects could unlock new therapeutic strategies, turning HMGB1 into a targetable asset in the fight against cancer.
The goal is not only to counteract its immunosuppressive effects but also to harness its immunoenhancing capabilities, aiming for a balanced approach in cancer treatment.

HMGBiotech Srl can provide comprehensive information to facilitate informed decision-making for research involving HMGB1.
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