Functional assays with TILs isolated from the tumor bed have identified a number of defects, including (i) absent (or low) expression of the CD3 zeta chain (CD3ζ), which is the key signaling molecule in the T-cell receptor pathway [38], (ii) decreased proliferation in response to mitogens or IL-2 [38], (iii) the inability to kill tumor cell targets [44, 45], (iv) an imbalance in the cytokine profile, with the striking absence of IL-2 and/or IFN-γ production [46], and (v) evidence of pronounced apoptotic features in a considerable proportion of TILs [38, 47]. This evidence concerns the gene IFNG and neoplasm.