De novo induction of intratumoral lymphoid structures and vessel normalization enhances immunotherapy in resistant tumors

Anna Johansson-Percival, Bo He, Zhi Jie Li, Alva Kjellén, Karen Russell, Ji Li, Irma Larma, Ruth Ganss

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

The tumor microenvironment confers profound resistance to anti-cancer immunotherapy. By targeting LIGHT, a member of the TNF superfamily of cytokines, to tumor vessels via a vascular targeting peptide (VTP), we developed a reagent with the dual ability to modulate the angiogenic vasculature and to induce tertiary lymphoid structures (TLSs). LIGHT-VTP triggered the influx of endogenous T cells into autochthonous or syngeneic tumors, which are resistant to immunotherapy. LIGHT-VTP in combination with checkpoint inhibition generated a large number of intratumoral effector and memory T cells with ensuing survival benefits, while the addition of anti-tumor vaccination achieved maximal therapeutic efficacy. Thus, the combination treatments stimulated the trafficking of pre-existing endogenous effector T cells as well as their intratumoral activation and were more successful than current immunotherapies, which fail due to tumor-intrinsic resistance mechanisms.

Original languageEnglish
Pages (from-to)1207-1217
Number of pages11
JournalNature Immunology
Volume18
Issue number11
DOIs
Publication statusPublished - 18 Oct 2017

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