TNF and neoplasm: Compared with CD3ζ-based second-generation CARs, T cells modified with the natural killer group 2D (NKG2D) ectodomain combined with 4-1BB and the DAP12 signaling domain released lower levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) during tumor cell lysis without a significant difference in tumor-killing effects both in vitro and in vivo [148].