Together, our data here demonstrate that blockade of HPK1 kinase activity could simultaneously address several key challenging factors in current immunotherapy (e.g. immune suppressive TME/immune evasion, dysfunctional T effector cells and NK cells, impaired tumor antigen presentation, primary and adaptive immune resistance), and it is likely that HPK1 inhibition will synergize with modulators of immune checkpoints as well as targets related to the PGE2 and adenosine pathways. This evidence concerns the gene MAP4K1 and neoplasm.