These ICRs generate a pro-inflammatory signal upon binding to an anti-inflammatory cytokine, thereby alleviating the immunosuppressive TME.37,55,56 Recently, an IL-4/IL-15 ICR, consisting of an IL-4 receptor extracellular domain and an IL-15 receptor transmembrane domain and endodomain, in combination with an NKG2D-CAR demonstrated improved antitumor activity of the CAR-T cells against pancreatic cancer in vivo.55 The IL-4/IL-15 CAR showed reduced T-cell exhaustion in the TME, increasing the CAR-T-cell efficacy. The gene discussed is IL4; the disease is pancreatic neoplasm.