Taken together, our investigation suggests that, whereas Vδ2+ cells are phenotypically homogeneous between healthy and tumor tissues, a portion of tumor-infiltrating Vδ2− cells present a unique phenotype involving the expression of markers associated to both early activated (CD28 and CD27) and experienced effector cells (CD57, PD-1 and 4-1BB). Here, CD28 is linked to neoplasm.