Cancer immunotherapy has become a new generation of anti-tumor treatment, but its indications still focus on several types of tumors that are sensitive to the immune system. Therefore, effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy. Natural products are reported to have this effect on cancer immunotherapy, including cancer vaccines, immune-check points inhibitors, and adoptive immune-cells therapy. And the mechanism of that is mainly attributed to the remodeling of the tumor-immunosuppressive microenvironment, which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy. Therefore, this review summarizes and concludes the natural products that reportedly improve cancer immunotherapy and investigates the mechanism. And we found that saponins, polysaccharides, and flavonoids are mainly three categories of natural products, which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment. Besides, this review also collected the studies about nano-technology used to improve the disadvantages of natural products. All of these studies showed the great potential of natural products in cancer immunotherapy.

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68+ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

UNASSIGNED: Inhibition of the programmed death ligand 1, programmed death 1 pathway has been successfully used for treatment of multiple advanced adult cancers. However, its use in pediatric osteosarcoma is still in its infancy. In this study, we investigated programmed death ligand 1 and other checkpoint molecules\' expression to determine the potential usefulness as targets for drug therapy.
UNASSIGNED: We incubated human wild-type osteosarcoma cells with incremental concentrations of doxorubicin to create a doxorubicin-resistant cell line. Matrigel in vitro invasion assays were used to compare invasiveness. Comparative programmed death ligand 1 expression was evaluated by Western blot assays. An immuno-oncology checkpoint protein panel was used to compare concentrations of 16 other checkpoint molecules. Chi-square tests and Wilcoxon rank-sum tests were used to determine significant differences.
UNASSIGNED: A doxorubicin-resistant cell line was successfully created and was significantly more invasive than wild-type cells (0.47 vs 0.07, P < .001). On Western blot assay, doxorubicin-resistant but not wild-type cells expressed programmed death ligand 1. Doxorubicin-resistant cells had significantly higher levels of T-cell immunoglobulin-3 and cluster of differentiation 86 and higher cluster of differentiation 27, cluster of differentiation 40, lymphocyte-activation gene-3, cluster of differentiation 80, programmed death ligand 1, programmed death ligand 2, and inducible T-cell costimulatory expression than wild-type cells. Both lines expressed B- and T-lymphocyte attenuator, cluster of differentiation 28, herpesvirus entry mediator, and programmed death 1. Herpesvirus entry mediator, cluster of differentiation 40, and programmed death ligand 2 were also present in the culture media of both cell lines.
UNASSIGNED: Doxorubicin-resistant osteosarcoma seems to express higher programmed death ligand 1 than nonresistant wild-type cells. Benchmarking checkpoint molecules may provide the basis for future studies that elucidate pathways of drug resistance and tumor metastasis, biomarkers for cancer prognosis or recurrence, and future targets for directed drug therapy.