The Ascomycete fungus Cordyceps sinensis is a complex of sclerotia (worm type) and progeny (grass type) and grows on the larvae of bat moths from the family Hepialidae infected with Hirsutella sinensis, the anamorphic form of C. sinensis. C. sinensis is a rare species that grows only on the Qinghai Tibet Plateau and has been used in China for thousands of years [1-2]. According to the Chinese pharmacopoeia, C. sinensis has a sweet taste and smooth properties, enters the lung and kidney meridians and has the effect of notifying the lung and kidney, stopping bleeding, and reducing phlegm. In the 1980s, Prof. Shen first isolated a strain of H. sinens is that reproduces asexually and developed it into health care products and medicines, such as the Bailingcapsule . These are mainly used for the treatment of lung and kidney diseases and for health care as a substitute for C. sinensis. The products have produced benefits for many patients at an inexpensive price. In recent years, with the increasing incidence of cancer in China, it has been used widely in cancer patients because of its nourishing effects. The purpose of this study is to review the anti-tumor applicationsof C. sinensis, especially for natural C. sinensis and the artificial fermentation of H .sinensis, to provide a basis for further guidance in its use in precision clinical medicine.
Cancer; Combined therapy; Cordyceps sinensis; Hirsutella sinensis; Immune system
It has been reported that water-based extracts of C. sinensis or H. sinensis (1.5-6mg/mL calculated according to materials) can inhibit the growth of a variety of tumor cells in vitro, including lung, gastric, liver and ovarian cancer cells [4-5]. The mechanism has undergone a preliminary exploration, and it was found that the extract primarily blocks the S-phase of the cell cycle . The growth and metastasis of gastric cancer, breast cancer, Lewis lung cancer and laryngeal cancer were also inhibited in vivo. The extracts can inhibit carcinogenesis of the anterior gastric epithelium in mice. C. sinensis has stronger anti-tumor effects than artificially fermented H. sinensis . In addition, a clinical case report indicated that C. sinensis has a good direct therapeutic effect on patients with advanced cancer . However, one study showed that C. sinensis promotes the growth of liver cancer in juvenile male mice, although it still has an inhibitory effect on female mice, possibly related to its androgen-like effects .
Although radiotherapy and chemotherapy have positive therapeutic effects on many advanced cancer patients, their inhibitory effects on the bone marrow and immune system and other toxic side effects are disturbing. In the clinic, it is clear that C. sinensis and H. sinensis reduce the side effects of chemotherapy and radiotherapy and can quickly ameliorate vomiting, nausea, poor appetite, hair loss, insomnia and other symptoms following radiotherapy and chemotherapy. This improvement is mainly related to the effect of the products on the immune system [9-12]. Cordyceps can rapidly repair damaged immune function and promote bone marrow rebuilding, significantly improve the phagocytic activity of the mononuclear–macrophage system and promote platelet production and hematopoiesis . Cordyceps can stimulate the proliferation of T and B cells and also stimulate the proliferation of spleen and thymus cells . In treated mice, the volume of the white pulp of the spleen and the size of the spleen body increases, thereby increasing the DNA content of the organand promoting the formation of antibodies. Therefore, Cordyceps can enhance the immune function of the human body by improving the overall levels of immune molecules and improving resistance to the side effects of chemotherapy, an outcome worthy of clinical promotion.
In recent years, tumor immunotherapy has brought new hope to patients with tumors, but immune tolerance is currently the biggest problem that hinders the clinical application of tumor immunotherapy. The production of terminal exhausted T cells is the key to immune tolerance, and systemic immune system activation is helpful for treatment with PD-1 inhibitors. The combined use of Cordyceps and immune-checkpoint inhibitors has not been reported, but our latest research has predicted that there may be significant advantages in combining Cordyceps with tumor immunotherapy. These advantages include promotion of the infiltration and activation of T cells in the tumor microenvironment, increases in the ratio of effect or memory T cells and inhibition of the production of terminal exhausted T cells [15,16]. We found that Cordyceps showed a strong anti-tumor effect in an in situ 4T1 excised lung metastasis model. The model was an important window into immunopotentiator treatment 1 week after surgery for the tumor immunosuppressant microenvironment disappearing briefly, and Cordyceps indicated a powerful tumor killing function following the activation of T cells.
In summary, the most significant effect of Cordyceps lies in the systematic promotion of T-cell generation, infiltration, and activation. If used in combination with immune checkpoint suppression, the treatment is clinically promising and may significantly affect immune checkpoints.