The key cellular component of solid tumors, including gliomas, are tumor-associated fibroblasts (TAFs), which support the growth of malignant cells, stimulate their invasion and metastasis, induce chemoresistance and suppress the antitumor immune response. TAFs are formed from resident stromal cells under the influence of the tumor cell secretome, including growth factors, chemokines, and extracellular vesicles. Communication between malignant cells and TAFs occurs through direct cell-cell contacts and by mutual exchange of secreted molecules and membrane vesicles. In this work, apoptotic bodies (apoBD) were obtained from two types of glioma cells (T98g cell line and cells isolated from glioblastoma patient biopsy) and characterized by surface markers. The surface of tumor apoBD contains glioblastoma tumor-associated markers such as ganglioside GD2 and antigen A2B5. It was demonstrated that glioma apoBDs have decreased levels of dont eat me molecules and increased level of eat me signal compared to the original intact glioma cells. On the one hand, glioma apoBDs reduced the viability of normal dermal fibroblasts in a dose-dependent manner, but on the other hand, induced their transformation into the inflammatory subtype of TAFs. The iTAFs obtained in this way demonstrated enhanced transcription of genes encoding cytokines, chemokines and growth factors, including IL17A, IL18, IL33, IFN-γ, CCL3, CCL5, CXCL1, CXCL5, CXCL10, CXCL12, TGFB1, and TNF, responsible for maintaining both tumorigenesis itself and the ability of fibroblasts to maintain it. It was found that glioma apoBDs are able to transfer tumor-associated markers, ganglioside GD2 and antigen A2B5, into normal fibroblasts, and the effects of anti-GD2 ADC on TAFs were investigated. This result may become a prerequisite for the development of targeted drugs that are effective not only against tumor cells but also against tumor stroma.
Kovalskaya et al. (Wed,) studied this question.