Table 1B.

Primary resistance – tumor extrinsic mechanism.

Mechanism	Cause	Consequences	Citation
Infiltration of immune suppressor cells	Macrophages Low-density circulating neutrophils	Support neoplastic cell survival, proliferation, angiogenesis, and immune suppression Suppress therapy-induced T cell expansion and effector function	(53, 56–61) (62, 63)
Induction of co-inhibitory molecules expression	Upregulation of CTLA-4, IDO, TIM-3, LAG-3, CD73, and VISTA	Inhibit the function of anti-tumor T cells and dendritic cells	(64–72)