HLA-C and neoplasm: Tspans can promote or inhibit tumor invasion and metastasis by interacting with the tumor cell microenvironment, Tspans induce immune responses to tumors in a context-dependent manner, and they can directly influence immune-cell signaling by interacting with key immune receptors (e.g., MHC molecules, CD4, CD8, CD19), Tspan protein family directly impacts immune-cell signaling, influencing antigen presentation, immune-cell migration, cytokine production, as well as T cell proliferation, activation, and subpopulation differentiation (Fig. 4).