Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment

► A T cell-inflamed tumor microenvironment may be predictive of response to immunotherapies. ► Non-inflamed tumors may require interventions directed at promoting chemokine production and T cell recruitment into tumor sites. ► T cell-infiltrated tumors appear to escape via the dominant action of immune suppressive mechanisms. ► Strategies to interfere with PD-L1/PD-1 interactions, block IDO activity, depleted Tregs, and reverse T cell anergy have been validated in animal models and are being tested clinically. ► Anti-PD-1 and anti-PD-L1 mAbs have shown impressive clinical activity in early phase clinical trials.