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This acidic environment not only directly suppresses the function of CD8 + T cells, but also acts through the following mechanisms: activation of the MAPK/Erk and NF-κB signaling pathways in CAFs, promotion of ECM-remodeling proteins (e.g., MMP-9), and stabilization of HIF-1α expression, thereby sustaining a tumor-promoting microenvironment

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HIV infection or retroviral replication e.g., HTLV I, HTLV-II, HTLV-III, etc