However, this single treatment was likely to promote PD-1 expression and thus dampen its efficacy, considering that (1) M1 macrophage-released factors may boost CD8+ T cell activation, which enhances the induction of PD-1 expression;46 and (2) IFN-β can stimulate tumor cells to release kynurenine (Kyn) and the latter induces PD-1 upregulation by CD8+ T cells via AhR activation.47 Indeed, we found that upon MTX-MP treatment, PD-1 expression was upregulated in both mesenteric lymph node and peripheral blood CD8+ T cells (Fig. 7e). This evidence concerns the gene CD8A and neoplasm.