We have previously shown that immunization with tumor antigen-loaded dendritic cells (DCs) and the immunomodulating drug, lenalidomide, synergistically potentiates the enhancing antitumor immunity in a myeloma mouse model. In this study, we investigated the immunogenicity of DCs combined with pomalidomide and dexamethasone in a myeloma mouse model. MOPC-315 cells were injected subcutaneously to establish myeloma-bearing mice. Four test groups were used to mimic clinical protocol: (1) PBS control, (2) DCs, (3) pomalidomide + dexamethasone, and (4) DCs + pomalidomide + dexamethasone. The combination of DCs plus pomalidomide and dexamethasone displayed greater inhibition of tumor growth compared to the other groups. This effect was closely related with reduced numbers of immune suppressor cells including myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells, with the induction of immune effector cells such as CD4+ and CD8+ T cells, memory T cells, natural killer (NK) cells, and M1 macrophages, and with the activation of T lymphocytes and NK cells in the spleen. Moreover, the level of the immunosuppressive factor vascular endothelial growth factor was significantly reduced in the tumor microenvironment. The collective findings in the murine myeloma model suggest that tumor antigen-loaded DCs combined with pomalidomide and dexamethasone synergistically enhance antitumor immunity by skewing the immune-suppressive status toward an immune-supportive status.
• Culture DCs with GM-CSF + IL-4 + IL-15 (IL-15 DCs) can be shortened for 6 days. • IL-15 DCs showed high expression levels of costimulatory receptors, IFN-γ and IL-12p70. • IL-15 DCs showed strong stimulation toward T, CIK and NK cells. • The activated lymphocytes showed high cytotoxicity against myeloma cells.
Carfilzomib is mainly used to treat multiple myeloma. Several side effects have been reported in patients treated with carfilzomib, especially those associated with cardiovascular events, such as hypertension, congestive heart failure, and coronary artery disease. However, the side effects, especially the manifestation of cardiovascular events through capillaries, have not been fully investigated. Here, we performed a pilot experiment to monitor peripheral vascular dynamics in a mouse ear under the effects of carfilzomib using a quantitative photoacoustic vascular evaluation method. Before and after injecting the carfilzomib, bortezomib, and PBS solutions, we acquired high-resolution three-dimensional PAM data of the peripheral vasculature of the mouse ear during each experiment for 10 h. Then, the PAM maximum amplitude projection (MAP) images and five quantitative vascular parameters, i.e., photoacoustic (PA) signal, diameter, density, length fraction, and fractal dimension, were estimated. Quantitative results showed that carfilzomib induces a strong effect on the peripheral vascular system through a significant increase in all vascular parameters up to 50%, especially during the first 30 min after injection. Meanwhile, bortezomib and PBS do not have much impact on the peripheral vascular system. This pilot study verified PAM as a comprehensive method to investigate peripheral vasculature, along with the effects of carfilzomib. Therefore, we expect that PAM may be useful to predict cardiovascular events caused by carfilzomib.
Rationale and patient concerns: We report on a 67-year-old woman who experienced drowsy mental status, facial numbness, and hearing loss on the right side; the symptom gradually worsened over the last 4 years. Brain magnetic resonance imaging revealed a 4.8 × 1.8 × 2.6 cm lesion located in the right cerebellopontine angle. Interventions: She underwent surgery with the retrosigmoid suboccipital approach and support from the digital robotic exoscope Synaptive Modus V system. To the best of our knowledge, this is the first reported case that used the robotic exoscope system in Vietnam, and also in Asia. Diagnosis: We performed radical resection of the tumor, the surgery position and the pathology result concluded the diagnosis was trigeminal schwannoma. Outcomes: After 30 months of follow-up, she fully recovered and the magnetic resonance imaging showed radical resection of the tumor. Lessons: The aim of this study is to share our experience with the robotic exoscope system, which can improve optical field and image resolution, hence creating an opportunity for surgery that otherwise is impossible. The application of this robotic exoscope system is a breakthrough in neurosurgery in developing countries, such as Vietnam.
18 August 2024 in Hematology, Transfusion and Cell Therapy