On August 4, professors Zhou Rongbin and Jiang Wei of the Faculty of Life Sciences and Medicine of the University of Science and Technology of China collaborated with the team of Tang Renhong of the State Key Laboratory of Translational Medicine and Innovative Drugs to publish a research paper online in the journal Science, and found that the hypothalamic-pituitary axis and the hormone α-MSH produced by it can promote the production of myeloid hematopoiesis and immunosuppressive myeloid cells through its receptor MC5R, thereby promoting tumor growth, and MC5R is expected to become a potential new target for tumor immunotherapy.
Schematic diagram of the mechanism of pituitary hormone inhibition of tumor immunity Provided by the research group
Tumor immunotherapy has become the fourth largest treatment for tumors after surgery, radiation therapy and chemotherapy. Tumor suppression of the immune system is an important reason for its evasion of immune system surveillance. Tumor immune checkpoint therapy can “reverse” immunosuppression to a certain extent and achieve good treatment results, but the clinical response is still relatively low. Only about 20% of patients currently benefit from this approach. Therefore, it is necessary to further reveal the tumor immunosuppressive mechanism and find new immunotherapy targets and strategies.
Tumor patients often suffer from mental or emotional stress such as depression, fear, anxiety, and epidemiological studies have found that long-term depression and stress can accelerate the development of tumors and weaken the effect of tumor immunotherapy, indicating that the nervous system and its mediated stress response play an important role in tumor growth and immune regulation.
In this study, the researchers studied the role of the neural stress sensing center in tumor immunity by constructing different tumor models and found that tumor-bearing mice were activated by hypothalamic neurons and that serum pituitary hormone α-MSH concentrations were significantly increased. Further research found that the α-MSH produced by the pituitary gland can promote myelination hematopoiesis and immunosuppressive myeloid cell production through its receptor MC5R, thereby promoting tumor growth. Blocking MC5R with an inhibitor inhibits tumor growth, and the inhibitor can exert synergistic effects with immune checkpoint drugs.
Finally, using clinical specimens, the researchers found that serum concentrations of α-MSH in patients with non-small cell lung cancer and malignant head and neck cancer were significantly increased and positively correlated with the proportion of myeloid immunosuppressive cells in the peripheral blood.
The innovation of this study is reflected in three aspects: the discovery of a neuroendocrine pathway that mediates tumor immunosuppression, the hypothalamic-pituitary-bone marrow (HPB) axis; Found MC5R as a new stress receptor that senses hypothalamic-pituitary signals, thereby promoting medullary hematopoiesis; Mc5R was found to be a potential new target for tumor immunotherapy.
The reviewers believe that the work is “very interesting”, “highly innovative and clinically relevant” and “can provide potential new avenues of immunotherapy”.
Zhou Rongbin said that in the next step, the team will continue to screen and identify new immune receptors that sense damage/stress signals in the body, revealing their immune and disease mechanisms; On the other hand, therapeutic drugs with immune intervention functions will be developed around targets such as MC5R. (Source: China Science Daily Wang Min)
Related paper information:https://doi.org/10.1126/science.abj2674