TNF and neoplasm: In another preclinical study by Goding et al., tumor-specific CD4 T cells were investigated and showed considerable upregulation of several co-inhibitory receptors (PD-1, TIM-3, lymphocyte-activation gene-3 (LAG-3), 2B4 and T cell immunoreceptor with Ig and ITIM domains (TIGIT)), accompanied by reduced effector cytokine expression [IFN-γ and tumor necrosis factor-α (TNF-α)] [65].