LIGHTing CAR T in the tumor microenvironment

Adoptive cell therapy using T cells expressing chimeric antigen receptors (CAR T) has demonstrated remarkable efficacy in hematological malignancies. However, CAR T therapy has shown limited responses in solid tumors, which may be due to inefficient CAR T cell recruitment, activation, and survival inside the suppressive tumor microenvironment (TME). The expression of the tumor necrosis factor superfamily member 14 (TNFSF14 or LIGHT) inside the TME promotes the expression of chemokines to form tertiary lymphoid structures (TLSs), which improves the recruitment and expansion of T cells as well as resistance to the suppressive TME. 1 Yu P. Lee Y. Liu W. Chin R.K. Wang J. Wang Y. Schietinger A. Philip M. Schreiber H. Fu Y.X. Priming of naive T cells inside tumors leads to eradication of established tumors. Nat. Immunol. 2004; 5: 141-149 Crossref PubMed Scopus (304) Google Scholar In this issue, Zhang et al. engineered LIGHT-expressing CAR T cells, resulting in the accumulation of the LIGHT-CAR T cells and potent tumor killing activities in both syngeneic and xenograft mouse models. 2 Zhang N. Liu X.H. Qin J.L. Sun Y. Xiong H. Lin B.X. Liu K.X. Tan B.H. Zhang C.L. Huang C.S. et al. LIGHT/TNFSF promotes CAR-T cell trafficking and cytotoxicity through reversing immunosuppressive tumor microenvironment.. Mol. Ther. 2023; 31: 2575-2590 Abstract Full Text Full Text PDF Scopus (1) Google Scholar LIGHT/TNFSF14 promotes CAR-T cell trafficking and cytotoxicity through reversing immunosuppressive tumor microenvironmentZhang et al.Molecular TherapyJuly 4, 2023In BriefDu and colleagues established novel LIGHT/TNFSF14-secreting CAR-T cells that have significantly enhanced trafficking, cytotoxicity, and clinical potential to solid tumors through reconstituting normalized tumor vasculature and tertiary lymphoid structures (TLSs) in the tumor microenvironment. Full-Text PDF