The study revealed the key role of manganese elements/manganese ions in tumor immunity.

On August 24, Professor Jiang Jingfan of Peking University's School of Life/North University-Tsinghua Joint Center for Life Sciences, in collaboration with Professor Han Weidong of the Department of Biotherapy at the First Medical Center of the PLA General Hospital, published the latest results in the field of oncology immunology online in the form of Research Article.
2018 Nobel Prize in Physiology or Medicine for the clinical application of PD-1 and CTLA-4 antibodies.
, however, immuno-checkpoint inhibitors are only effective in about 20% of tumor patients, and how to improve the response of tumor patients to immunotherapy is a key issue that needs to be solved urgently.
recent studies have found that the activation of intracellular cGAS-STING pathlines, such as degenerate cells, plays a crucial role in resuscitation of the body's anti-tumor immune response.
many research institutions and pharmaceutical companies around the world are investing heavily in the search for exciting agents for the cGAS-STING path.
, however, are mostly complex, costly, and do not enter cells effectively, so treatment is not ideal.
In this study, Jiang's team first found that tumor cell growth in manganese-deficupulation mice significantly accelerated and tumor lung metastasis increased significantly, indicating that manganese, as a necessary trace element, plays an essential role in tumor immunity under physiological conditions.
Exogenetic addition of Mn2 plus can effectively activate the cGAS-STING path of human or mouse cells, significantly promote the host antigen delivery cells such as DC and M for tumor antigen delivery capacity, promote cytotoxic T cells in tumor tissue immersion and tumor-specific killing.
, on the other hand, Mn2 plus can significantly enhance the tumor killing ability of NK cells and promote the host's tumor immuno surveillance.
they tried to use Mn2 plus PD-1 antibodies ("manganese-free therapy") and found that Mn2 plus significantly enhanced the tumor treatment effect of PD-1 antibodies in a variety of tumor models.
Han for the East team completed the "manganese-free therapy" Phase I clinical results show that for a variety of recurrence difficult to treat or progress phase of endothyscopic tumors, Mn2 plus joint PD-1 inhibitor program obtained significant efficacy (objective mitigation rate of 45.5%, disease control rate of 90.9%), and showed good clinical safety, the current program in the single disease phase II clinical trials are advancing in an orderly manner. The results of the
clinical study further show that the "loose brake" effect of immuno-checkpoint inhibitors (e.g. PD-1 antibodies) is relatively limited, and that by simultaneously "stepping on the accelerator" to promote the immune surveillance of tumor cells by the natural immune system, or by turning cold tumors into hot tumors, the response rate of tumor patients to treatment can be significantly improved.
addition, this study demonstrates that manganese element/manganese ions (Mn2 plus) play a vital role in anti-tumor immunity, opens up new ideas and treatment options for tumor immunotherapy (manganese-free therapy), and shows great clinical application prospects.
Because of the huge reserve of manganese, the two-price manganese solution preparation is simple, low cost, its transportation, storage is very convenient, these advantages make "manganese-free therapy" easy to apply and can significantly reduce the cost of cancer treatment, benefit patients and countries.
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