Tumor‐Associated Macrophage‐Derived Exosomal LINC01232 Induces the Immune Escape in Glioma by Decreasing Surface MHC‐I Expression

Abstract

Tumor-associated macrophage (TAM) infiltration facilitates glioma malignancy, but the underlying mechanisms remain unclear. Herein, it is reported that TAMs secrete exosomal LINC01232 to induce tumor immune escape. Mechanistically, LINC01232 is found to directly bind E2F2 and promote E2F2 entry into the nucleus; the two synergistically promots the transcription of NBR1. The increase in binding between NBR1 binding and the ubiquitinating MHC-I protein through the ubiquitin domain causes an increase in the degradation of MHC-I in autophagolysosomes and a decrease in the expression of MHC-I on the surface of tumor cells, which in turn led to tumor cell escape from CD8 + CTL immune attack. Disruption of E2F2/NBR1/MHC-I signaling with shRNAs or blockade with the corresponding antibodies largely abolishes the tumor-supportive effects of LINC01232 and inhibits tumor growth driven by M2-type macrophages. Importantly, knockdown of LINC01232 enhances the expression of MHC-I on the surface of tumor cells and improves the response to reinfusion with CD8 + T cells. This study reveals the existence of critical molecular crosstalk between TAMs and glioma mediates through the LINC01232/E2F2/NBR1/MHC-I axis to support malignant tumor growth, indicating that targeting this axis may have therapeutic potential.

TBX15 facilitates malignant progression of glioma by transcriptional activation of TXDNC5

“…Tumor associated macrophages (TAMs), the most abundant cell type in glioma tissues apart from parenchyma cells, play an important role in the malignant progression of glioma. 19 Immune infiltration analysis was conducted using TCGA as well as CGGA data, which showed significantly greater infiltration of M2 macrophages in the TBX15 high glioma tissues compared to the those with low TBX15 expression ( Figures 3 A and 3B). To investigate the potential involvement of TBX15 in TAM polarization, we induced THP-1 cells with phorbol 12-myristate 13-acetate (PMA) to differentiate them into macrophages and co-cultured the latter with glioma cells in transwell chambers.…”

Exosome‐transmitted podoplanin promotes tumor‐associated macrophage‐mediated immune tolerance in glioblastoma

“… 11 Conversely, tumor‐associated macrophage‐derived exosomal LINC01232 induces immune escape in glioma by downregulating surface MHC I expression. 54 Therapeutically, targeting PDPN with CAR‐T cells and antibodies has been explored in preclinical research. For example, combination therapy of cancer‐specific anti‐PDPN CAR‐T cells with oncolytic herpes virus inhibited tumor growth and improved survival in GBM.…”

“…In addition, studies have shown that tumor‐derived exosomes coated with miR‐3591‐3p induce M2 polarization of macrophages and promote the malignant progression of glioma 11 . Conversely, tumor‐associated macrophage‐derived exosomal LINC01232 induces immune escape in glioma by downregulating surface MHC I expression 54 . Therapeutically, targeting PDPN with CAR‐T cells and antibodies has been explored in preclinical research.…”

KIAA0040 enhances glioma growth by controlling the JAK2/STAT3 signalling pathway

“…For further details, we direct readers to the pertinent documentation for comprehensive solutions. 22 , 23 , 24 …”