Fig. 2.

Immune evasion orchestrated by tumour cells and the tumour microenvironment. PDAC cells release cytokines and recruit immunosuppressive cells, including myeloid cells, regulatory T cells and γδT cells, which inhibit the function of effector T cells. Tumour cells also promote the activation of stromal fibroblasts by producing ligands, such as SHH. Activated fibroblasts not only enhance the growth of tumour cells, but also inhibit effector T cells through several different mechanisms, including the deposition of extracellular matrix to impede T cell trafficking, excretion of cytokines to suppress T cells activity, and induction of immunosuppressive myeloid cells directly with cytokines or indirectly through the recruitment of suppressive B cells. Some of the immune infiltrates, including suppressive B cells and myeloid cells, also produce growth factor ligands or cytokines to directly stimulate tumour growth. Metabolite changes in the tumour microenvironment also contribute to the inhibition of T cell activation, including depletion of glucose, arginine and tryptophan and the accumulation of lactate and kynurenine. Treg: regulatory T cells, ECM: extracellular matrix, CAFs: cancer-associated fibroblasts, Teff: effector T cells, MDSC: myeloid-derived suppressor cell; TAM: tumour-associated macrophage.