Figure 2.

How the ECM affects the efficacy of immunotherapy. (A) The dense ECM can prevent immune cells to reach the tumor cells even in highly immunogenic cancers. Upon contact with areas of increased stiffness, lymphocytes are prone to follow less a chemoattractive gradient but to migrate along the fields of elevated rigidity (haptotaxis). (B) The shielding diffusion barrier that the ECM forms prevents also immunotherapeutic drugs, like checkpoint inhibitory ABs, to reach the tumor. (C) The increased hypoxia that results from poor supply behind the diffusion barrier can directly enhance immune escape by upregulation of immunomodulatory factors like IL-10 or TGF-β. (D) Hypoxia also increases angiogenic signals. Activated blood vessels show reduced ICAM1 expression, impeding attachment and extravasation of immune cells.