It is reported that tumor immunotherapy has become the fourth largest tumor treatment method after surgery, radiotherapy and chemotherapy. The suppression of the immune system by tumors is an important reason for their evasion of immune system surveillance. Tumor immune checkpoint therapy can “reverse” immunosuppression to a certain extent and achieve better therapeutic effects, 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.
Cancer patients often suffer from mental or emotional stress such as depression, fear, and 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 It plays an important role in tumor growth and immune regulation.
In this study, the researchers investigated the role of neural stress-sensing centers in tumor immunity by constructing different tumor models, and found that hypothalamic neurons in tumor-bearing mice were activated, and the serum concentration of the pituitary hormone α-MSH was significantly increased . Further studies have found that α-MSH produced by the pituitary can promote the production of myeloid hematopoietic and immunosuppressive myeloid cells through its receptor MC5R, thereby promoting tumor growth. Blocking MC5R with an inhibitor can inhibit tumor growth, and the inhibitor can work synergistically with immune checkpoint drugs. Using clinical specimens, the researchers found that serum α-MSH concentrations in patients with non-small cell lung cancer and malignant head and neck cancer were significantly elevated and positively correlated with the proportion of myeloid immunosuppressive cells in peripheral blood.
The innovation of this study is reflected in three aspects: the discovery of a neuroendocrine pathway that mediates tumor immunosuppression, namely the hypothalamic-pituitary-bone marrow (HPB) axis; the discovery of MC5R as a new stress receptor that senses the hypothalamus – Pituitary signaling to promote myeloid hematopoiesis; MC5R was found to be a potential new target for tumor immunotherapy.
The reviewers considered the work “very interesting”, “highly innovative and clinically relevant” and “could offer potential new avenues for 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, and reveal their immune and disease mechanisms; therapeutic drugs.