GZMB and neoplasm: The functional initiation of TRM cells requires the activation of co-stimulating TCR signals, including E-cadherin-CD103, extracellular signal-regulated kinase1/2-phospholipaseCγ1, phosphoinositide-3-kinase-AKT, proline-rich tyrosine kinase 2, and paxillin (Pxn).228,634,635 Activated TRM cells produce cytotoxic molecules, including GZMB, perforin, and IFN-γ, and upregulate 4-1BB, CD27, and Ki67 expression, sustaining anti-tumor activities.197,636 Many cytokines engage in regulating the immune abilities of TRM cells.