Estado imune periférico em doentes com sarcoma de tecidos moles submetidos a quimioterapias baseadas em trabectedina versus antraciclinas
Year: 2021
Type: dissertation
Study design: Observational Study
Abstract: The assessment of the immunological status of cancer patients has been the focus of several studies. Yet, its prognostic value in soft tissue sarcomas (STS) remains unclear. In addition, most studies focused only on the analysis of the tumor microenvironment (TME) and did not consider patient therapy. The present study analyzed peripheral blood from patients with STS in order to compare the effects of trabectedin with anthracycline-based therapy on the immunological status. To better understand the immunomodulatory role of trabectedin-based therapies, we assessed the immunological status considering the duration of therapy (>20 cycles versus ≤20 cycles). In addition, the predictive role of the peripheral immune elements, considering the patient therapy, was also evaluated.We analyzed the repertoire and frequency of immune cells using flow cytometry, the expression of immune-related genes was performed by real-time PCR, and the quantification of soluble immune-related factors by Multiplex Analyte Profiling (xMAP®) tecnology.The results showed differences in the immunological status of STS patients when the therapies and the number of trabectedin cycles were compared. The levels of double-negative T cells activated CD4 T cells, memory regulatory T cells, PD-1 Natural Killer cells, and the expression of IL1B, FCGR3A, and SELL were found increased in the group of patients who had undergone trabectedin-based therapy, when compared to anthracycline-based therapy. On the contrary, the levels of naïve CD4 T cells, early myeloid-derived suppressor cells (e-MDSC), and the expression of CCL3 and CCL4 were found decreased. When we analyzed the patients on long-term trabectedin therapy (>20 cycles), the frequencies of CD56dim Natural Killer (NK) cells and double-positive T cells, the levels of soluble programmed death-ligand 2 (PD-L2) and B7-H2, and the expression of CXCL1 were found increased when compared with ≤20 cycles of trabectedin. Contrary, plasmacytoid dendritic cells, activated CD3brigh Natural Killer T-like cells, and the expression of FGF2 were decreased. Concerning the prognostic value of the immune-related factors statistically altered, we found that higher levels of the soluble immune checkpoints PD-L2 and B7-H2 were correlated with longer overall survival. In conclusion, these results suggest an impact of trabectedin-based therapy on the immunological status of STS patients. Moreover, the levels of PD-L2 and B7-H2 in plasma could be used as good predictive biomarkers for STS patients undergoing long-term trabectedin therapy. Further studies with a larger number of patients will be necessary to confirm the preliminary data of the present study.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7042429027