Hematopoietic progenitor kinase 1 (HPK1), also termed as mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1), is a serine/threonine kinase that mainly expressed in hematopoietic cells . As an immune negative regulator, HPK1 suppresses the transduction of multiple signaling pathways in immune cells, among which the regulatory role in T cell receptor (TCR) signaling pathway was mostly studied . Upon TCR stimulation, successive phosphorylations on Tyr381, Ser171 and Thr165 lead to the full activation of HPK1. Fully activated HPK1 then phosphorylates Src homology 2 domain containing leukocyte protein of 76 kDa (SLP76), a component of TCR signalosome, at Ser376. This process further causes the destabilization of TCR signalosome, and as a consequence, the transduction of TCR signaling is attenuated . Early knockout studies demonstrated that HPK1deficient mice showed enhanced T cell proliferation, increased T helper type 1 (Th1) cytokine (e.g., IL-2, IFN-γ) production, and improved dendritic cell-mediated antigen presentation . Later studies using HPK1 kinase-dead mice emphasized the predominant role of HPK1 kinase activity in regulating T cell function, and co-blocking the kinase activity of HPK1 and PD-1/PD-L1 axis could bring a synergetic antitumor effect in murine colon adenocarcinoma model . Furthermore, T cells from the genetic engineered mice were resistant to immune suppression mediated by PGE2 and adenosine . Given these compelling evidences, together with the numerous successful cases in kinase drug discovery, HPK1 has been proposed as a promising target in cancer immunotherapy.