Significance of trogocytosis and exosome-mediated transport in establishing and maintaining the tumor microenvironment in lymphoid malignancies

Abstract

The tumor immune microenvironment has been focused on in both solid and hematological tumors. Bystander cells in lymphoid malignancy are important for the progression of tumors. 1 Immune cells around the tumor contribute to the pro-tumor immunity, and support the survival and progression of the tumor as a niche. Immune cells are currently targeted for immunotherapy, for example, chimeric antigen receptor (CAR) -T cell therapy, 2 and immune checkpoint inhibitors such as anti-programmed cell death 1 (PD-1) antibody. 3 CAR-T cell therapy is particularly effective against hematological tumors. In the case of classic Hodgkin lymphoma (cHL), anti-PD-1 antibody is highly effective. This suggests that the immune interactions between the tumor and its surrounding cells are important for the progression of hematological tumors and their therapy.Intercellular communication tools, such as cytokines and chemokines, are important for educating tumor biology. Furthermore, intercellular transfer of molecules, such as via trogocytosis and exosomes, was recently reported to be involved in facilitating the interaction between the tumor and surrounding immune cells. [4][5][6][7] Although cytokines and chemokines induce gene expression of target cells, they must undergo signal transduction. Trogocytosis and exosomes mediate direct transfer of molecules from donor cells to target cells. 8 They may be able to control the function of target cells more rapidly than the induction of gene expression by cytokines and chemokines.In this article, we reviewed these biological phenomena functioning in lymphoid malignancy based on our findings. TROGOCYTOSISTrogocytosis is a phenomenon characterized by the directional movement of molecules between the interacting cells or towards the cells connected to a donor cell via the interchanging junctions of the plasma membrane. 9,10 In the 1970s, the proteins that were specifically expressed in one cell type were detected from the surface of other cell types. 11,12 The transfer of major histocompatibility complex (MHC) molecule from antigen-presenting cells (APCs) to

Unraveling the Immune Microenvironment in Classic Hodgkin Lymphoma: Prognostic and Therapeutic Implications

“…Interestingly, in cHL, PD-L1 is also expressed by TAMs which co-localize with HRS cells, thus augmenting the immunosuppressive signals against host immunity [ 11 , 63 , 99 ]. HRS cells have been shown to be capable of transferring PD-L1 molecules to TAMs’ surface via trogocytosis, a process that enables neighboring cells to exchange membrane molecules, which underlines the role of HRS cells in actively shaping their microenvironment to their benefit [ 100 ]. The immunosuppression via PD-1 interactions has provided the biological rationale for anti-PD1 blockade therapy with nivolumab or pembrolizumab, which, in HL, achieved the highest response rates among human malignancies.…”

Current progress of the tumor microenvironment in lymphoid malignancies

“…Dr. Kawashima, who identified trogocytosis as a new mechanism of the upregulation of PDL1, 3 summarized the mechanism of PDL1 expression along with the role of exosomes. 4 Dr. Ennishi, who identified the functional significance of TMEM30A alterations in DLBCL, 5 described the importance of CD47-mediated “don’t eat me” signaling in DLBCL through the role of TMEM30A. 6 Dr. Miyawaki summarized how comprehensive gene expression profiling clarified the significance of the tumor microenvironment in diffuse large B cell lymphoma and peripheral T-cell lymphoma, not otherwise specified, the most frequent lymphomas of B-cell and T-cell lineage, respectively (in press).…”