MFSD2A suppresses CD8+ T cell exhaustion in colorectal cancer by inhibiting ERK/p38 MAPK-PD-L1 signaling

Figure 2 Major facilitator superfamily domain containing 2A modulates the extracellular signal-regulated kinase/p38 mitogen-activated protein kinase-programmed death-ligand 1 axis and alleviates CD8+ T cell exhaustion. A: Western blotting analysis of extracellular signal-regulated kinase/p38 mitogen-activated protein kinase pathway and programmed death-ligand 1 expression in MC38 [overexpression negative control (oeNC), major facilitator superfamily domain containing 2A-overexpressing (oeMFSD2A)] and Caco-2 [siRNA negative control (siNC), major facilitator superfamily domain containing 2A-knockdown (siMFSD2A)] cells; B: The expression of programmed cell death protein 1 and cytotoxic T lymphocyte-associated antigen 4 in CD8+ T cells following co-culture of MC38 (control, oeNC, oeMFSD2A) cells or Caco-2 (control, siNC, siMFSD2A) cells with CD8+ T cells; C: Killing assay (24 hours) showing the lysis proportion of MC38 (control, oeNC, oeMFSD2A) cells and Caco-2 (control, siNC, siMFSD2A) cells co-cultured with CD8+ T cells, respectively; D: Following co-culture of MC38 cells (control group, oeNC group, oeMFSD2A group) or Caco-2 cells (control group, siNC group, siMFSD2A group) with CD8+ T cells, enzyme-linked immunosorbent assay assays were performed to detect the interleukin-2, interferon-γ, and tumor necrosis factor-α secreted by CD8+ T cells. ^aP < 0.0001 vs overexpression negative control, ^bP < 0.0001 vs siRNA negative control. oeMFSD2A: Major facilitator superfamily domain containing 2A-overexpressing; oeNC: Overexpression negative control; siMFSD2A: Major facilitator superfamily domain containing 2A-knockdown; siNC: SiRNA negative control; ERK: Extracellular signal-regulated kinase; MAPK: Mitogen-activated protein kinase; PD-L1: Programmed death-ligand 1; CTLA4: Cytotoxic T lymphocyte-associated antigen 4; IL-2: Interleukin-2; IFN-γ: Interferon-γ; TNF-α: Tumor necrosis factor-α.