Distinct human circulating NKp30 + FcεRIγ + CD8 + T cell population exhibiting high natural killer-like antitumor potential

Significance CD8+ T cell recognition of tumor cells is typically based on the detection of specific MHC–peptide complexes, while natural killer (NK) cell recognition relies on the detection of NK ligands by an array of NK receptors. In this study we uncovered a distinct small population of CD8+ T cells expressing NKp30, a potent activating NK receptor, on peripheral blood from healthy donors. Those innate-like CD8+ T cells, coexpressing FcεRIγ and PZLF, could be generated and differentiated from a population of peripheral blood CD8+ T cells as result of IL-15–driven acquisition of broad innate features. This unique effector population could potently control the growth of tumors in an NK-like manner, making it promising for cancer immunotherapy by its dual target-recognition potential.