Abstract:
Little is known about the potency of angiogenesis-associated genes (AAGs) in the regulation of the immune microenvironment of multiple myeloma (MM). Traditional Chinese medicine has positive anti-angiogenesis and immunomodulatory effects, especially in the treatment of tumors. Although frequently used in the clinic, the mechanism remains elusive in MM. In this study, we divided MM patients into three angiogenesis subgroups based on 35 AAGs, and these subgroups showed significant differences in clinical outcome, biological functions, immune infiltration, and immune checkpoints. These results suggest that AAGs are critical in screening immune molecular subtypes as well as the response to checkpoint immunotherapy. Therefore, we established an AAG_score model with 11 selected immunity- and prognosis-associated differentially expressed genes (DEGs) to quantify angiogenesis subgroups. There is a significant positive correlation between favorable prognosis-related molecules (LST1, IGHM, PD-L2, CD22, FUCA1, SLC7A7, and ADAM28) and the infiltration of most immune cells, while the relationship between risk-related molecules (NUF2, IFI16, and GEMIN6) and immune cell infiltration was the opposite. We also revealed that the expression of 11 molecules was negatively correlated with that of almost all immune checkpoints, indicating that these key molecules could mediate the formation of individual infiltration patterns of immune cells as well as the response to immune checkpoint blockade. In recent years, an increasing number of Chinese patients have tried traditional Chinese medicine (TCM) for complementary interventions following a hematologic malignant disease diagnosis, including MM. Previous studies have shown that TCM can regulate the immune system and angiogenesis. Therefore, we comprehensively analyzed the regulatory effects of Danggui-Sini decoction (DSD) on MM angiogenesis and the immune microenvironment on the basis of the AAG_score model. UHPLC?MS/MS and network pharmacology were performed to analyze its chemical constituents and targets coincident with the AAG_score model. Five AAG_score genes could be targeted by DSD. Furthermore, the in vitro and in vivo experiments demonstrated that DSD could inhibit angiogenesis promoted by the secretion of U266 cells and reduce tumor burden.Therefore, we concluded that angiogenesis has a great influence on the immune phenotype and that the AAG_score has the potential to help clinicians choose precise immune checkpoint blockade treatments. Future studies defining the mechanisms of monomers or a combination of ingredients in DSD on MM with anti-angiogenesis and immune modulate signatures will be of great value in basic research and transformation
Audience Take Away Notes:
- We constructed the AAG_score model to predict patient prognosis and evaluate the immune microenvironment, and this model presented great robustness and independence.
- Angiogenesis has a great influence on the immune phenotype and that the AAG_score has the potential to help clinicians choose precise immune checkpoint blockade treatments.
- DSD could inhibit MM angiogenesis and reduce tumor burden, further exploration of the antiangiogenic effect of DSD on immune modulation will provide new insights into how TCM controls tumor growth.
