Microparticles and PD1 interplay added a prognostic impact in treatment outcomes of patients with multiple myeloma

Abstract

Although multiple myeloma (MM) is still considered as an incurable disease by current standards, the development of several combination therapies, and immunotherapy approaches has raised the hope towards transforming MM into an indolent, chronic disease, and possibly achieving a cure. We tried to shed light on the expression of PD1 and different Microparticles (MPs) in MM and their interplay as a mechanism of resistance to standardized treatments, in addition, find their associations with prognostic factors of symptomatic MM. Thirty patients with newly diagnosed and chemotherapy naïve active MM, along with 19 healthy participants of comparable age and sex were recruited, after diagnosis of MM; blood samples were collected from both patients and controls for flow cytometric detection of CD4+, CD8+, CD4+PD1+, and CD8+PD1+T cells, total MPs, CD138+ MPs, and platelet MPs. MM patients had statistically significant higher levels of TMPs, CD138+ MPs compared to their controls, while PMPs exhibited no significant difference between both groups. Statistically significant higher percentages of CD8+, PD1CD8+, PD1CD4+T cells were detected in patients compared to controls, while the latter group had a significantly higher percentage of CD4+T cells than MM patients, patients who did not achieve complete response, had significantly higher percentages of PMPs, CD138+MPs, PD1+CD8+, PD1+CD4+, and CD8+T cells (cutoff values = 61, 10.6, 13.5, 11.3 and 20.1 respectively), (p-values = 0.002, 0.003, 0.017, 0.001 and 0.008 respectively). Microparticles and PD1 expressions were associated with proliferative potential and resistance to Bortezomib-based treatments, our results suggested that they played a crucial role in myeloma progression.