The incidence and mortality rates of tumors are increasing year by year and have become one of the major diseases threatening human health [[1], [2], [3]]. There are two main ways to treat tumors clinically: radiotherapy and chemotherapy, but both of them have serious side effects [[4], [5], [6]]. In the 1960s, Japanese scientists discovered that shiitake mushroom polysaccharides have anti-tumor activity with little toxic side effects. Since then, the anti-tumor activity of polysaccharides has become a hotspot and continues to the present day [7]. Polysaccharides tend not to inhibit tumor cells directly but play an anti-tumor function indirectly by activating the host immune response, which is an important reason why polysaccharides play a tumor-suppressing role with fewer toxic side effects [[7], [8], [9], [10], [11]]. A variety of polysaccharide drugs have been approved for the clinical treatment of tumors, such as shiitake mushroom polysaccharides, ginseng polysaccharides and Ganoderma lucidum polysaccharides [12].

Combinations of drugs are therapeutic tools with a long history, whose main purpose is to maximize drug efficacy and minimize adverse effects, leading to better efficacy [13]. In the treatment of tumors, chemotherapy is the most basic method, but its immunosuppressive side effects also bring great misery to tumor patients and even prevent them from further treatment [14,15]. Therefore, searching for adjuvant therapeutic agents with low toxicity and fewer side effects to reduce the adverse effects brought by chemotherapy and to improve anti-tumor efficacy has become a hot research topic in recent years. Chinese medicine has significant advantages in reducing the toxic side effects of chemotherapy, preventing tumor recurrence and metastasis [13]. Combining Chinese medicines with chemotherapeutic agents will both reduce the dose administered and the toxic side effects, thus enhancing the anti-tumor efficacy. Polysaccharide has many biological activities and low toxicity, so the combination of traditional Chinese medicine polysaccharide and chemotherapy drugs has attracted more and more attention [13,[16], [17], [18], [19], [20], [21]].

The complex tumor microenvironment (TME) includes interacting tumor cells, non-tumor cells (immune cells, endothelial cells, fibroblasts, etc.) and surrounding extracellular components (cytokines, growth factors, extracellular components, etc.) [22]. TME is often in a state of immunosuppression, which is beneficial to tumor growth and metastasis, and reduces the efficacy of chemotherapy drugs, thus becoming one of the key problems in clinical cancer treatment [22]. TAMs are an important part of the immune cell population in TME. TAMs have two main functional phenotypes: M1 and M2 [23,24]. Many studies have shown that TAMs have a two-way effect, in addition to the M1 phenotype having a certain anti-tumor effect, more often develop into the M2 phenotype to promote the occurrence and development of cancer [25,26]. Furthermore, M1 phenotype macrophages with tumor-killing effects are often transformed into M2 phenotype macrophages when TAMs are induced by tumor cells [27]. Therefore, it is of great research value to inhibit M2 phenotype macrophages in TME and increase M1 phenotype macrophages, so as to alleviate the immunosuppressive microenvironment in tumor tissue [28].

The rhizome of Menispermum dauricum DC (Menispermaceae), called BeiDouGen in Chinese, is a traditional Chinese medicinal herb that has been used widely in clinical practice for treating rheumatic arthralgia, dysentery, colitis, and sore throats [29]. It has been shown that crude polysaccharide from the rhizome of Menispermum dauricum DC has anti-ovarian cancer activity [30], enhances phagocytosis of mouse macrophages [31], counteracts or attenuates the mutagenic effect triggered by cyclophosphamide and mitomycin C [32]. Therefore, as an immune booster, the rhizome of Menispermum dauricum DC polysaccharide is expected to be used in the immunotherapy of tumor patients or as an adjuvant drug to repair the immune damage caused by radiotherapy and chemotherapy. MDP was a homogeneous polysaccharide obtained from the rhizome of Menispermum dauricum DC with a molecular weight of 6.16 × 103 Da. It had a main chain composed of (1 → 6)-α-d-Glcp and a terminal-α-d-Glcp side chain [33]. It was found that MDP could promote the proliferation and phagocytic activity of RAW264.7 cells, and it could significantly increase the content of IL-6 and TNF-α in the cell supernatant, with significant immunological activity [33]. On this basis, CTX was used to establish an immunosuppression model to investigate the in vivo immunological activity and mechanism of MDP, and RAW264.7 cells were used to further validate the immunological activity mechanism of MDP [33,34]. In addition, a Lewis lung cancer model was established to investigate the in vivo anti-tumor effects of MDP, the effects of MDP combined with CTX on increasing the anti-tumor effect and reducing the toxicity in vivo and its alleviating effect on the tumor immunosuppressive microenvironment, intending to lay the foundation for the development of the rhizome of Menispermum dauricum DC polysaccharide as a therapeutic or adjuvant drug for tumor treatment.