The perspectives of interleukin-10 in the pathogenesis and therapeutics of multiple myeloma

Abstract

Multiple myeloma (MM) is typically featured by the increased levels of inflammatory cytokines in the neoplastic plasma cells (PCs) producing monoclonal immunoglobulin. PCs proliferate in the bone marrow, which will lead to extensive skeletal destruction with osteolytic lesions, osteopenia, or pathologic fractures. The diagnostic biology of MM has progressed from morphology and low-sensitivity protein analysis into multiomics-based high-throughput readout, whereas therapeutics has evolved from single active agent to potential active drug combinations underlying precision medicine. Many studies have focused on the cytokine networks that control growth, progression, and dissemination of the disease. The complexity of cytokines in MM development remains to be elucidated comprehensively. Apart from knowing that interleukin (IL)-6 is important in the pathogenesis of MM, it has been shown that IL-6 is a paracrine factor supplied by the microenvironment comprising of those cells from the myeloid compartment. Due to IL-10 was considered an immunosuppressive cytokine to promote cancer escape from immune surveillance, the role of IL-10 in this regard has been underestimated although recent advances have reported that IL-10 induces both PC proliferation and angiogenesis in MM. In addition, cumulative studies have suggested that IL-10 plays an important role in the induction of chemoresistance in many cancers; a virtual requirement of autocrine IL-10 for MM cells to escape from an IL-6-dependent proliferation loop was implicated. In this review, we summarize the available information to elucidate a new understanding of the molecular and functional roles of IL-10 in MM.

Central Thromboangiitis Obliterans: A Case Report

“…The pathological feature of the disease is the presence of inflammatory thrombi in affected vessels; patients usually present with acute or chronic, ischemic or infectious acral lesions (2). Cerebrovascular complications are seldom observed (3,4). Herein, a case of thromboangiitis obliterans with central involvement was reported.…”

Communicator Extraordinaire: Extracellular Vesicles in the Tumor Microenvironment Are Essential Local and Long-Distance Mediators of Cancer Metastasis

“…In addition to the enhanced energy supply that the recruitment of stromal cells into the TME has, the infiltration of stromal cells has also extensively been shown to promote neo-angiogenesis [ 10 ], epithelial cell migration [ 11 , 12 ], and extracellular matrix remodeling [ 13 , 14 ]. Additionally, stromal influences are known to contribute significantly to both the evasion of immune surveillance and enhanced chemotherapeutic resistance of cancer cells [ 15 , 16 ], which are largely attributed to the increased production of several stromal derived chemokines, cytokines [ 17 , 18 ], that include tumor necrosis factor alpha (TNF-α) [ 19 ], interleukin-6 (IL-6) [ 20 ], transforming growth factor beta (TGF-β) [ 21 ], and interleukin-10 (IL-10) [ 22 ], and growth factors. In recent years, however, circulating extracellular vesicles and other types of extracellular vesicles have gained in importance with regards to the delivery and biological effects of their packaged cargo [ 23 , 24 , 25 ].…”