- Limited quantity of neo-epitopes(weak Signal-1 substrate)- Carcinoma tumor heterogeneity and dynamic mutational landscape (antigen poly-clonality and instability)- Antigen presenting cell (APC) paucity and tolerogenic bias- Sensitized CD8+ T cell shielding/suppression by tumor glycocalyx- Immune synapse suppression: A plethora of T-cell “brakes” and paucity of T-cell “accelerators”. Here, CD8A is linked to neoplasm.