Murine neonatal dermal fibroblast acquires a lymphoid tissue organizer cell-like activity upon synergistic activation of TNF-α receptor and LTβ receptor

Abstract

Tertiary lymphoid organs (TLOs) are ectopic aggregates of immune cells. As accumulating studies demonstrate TLOs as a predictor of better prognosis in certain cancers, targeting TLO formation, which is tightly regulated by the lymphoid tissue organizer cells (LTOs), has become intriguing in cancer treatment. However, the clinical outcome of these attempts is limited, because the approaches for activating tumor adjacent LTO is lack and little is known about what type of self-cell can be used as LTO to initiate TLO formation. Here we demonstrate that co-stimulation with membrane-bound ligand LTα₁β₂ and soluble TNF-α could induced an LTO-like activity in murine neonatal dermal fibroblast, featured by high expression of cell migration-associated chemokines and adhesion molecules that resemble typical LTO gene signature. Furthermore, the LTO-phenotypic dermal fibroblast could enhance the attachment and survival of T and B cell and proliferation of T cell. These findings suggest dermal fibroblast as a promising target for TLO induction to improve cancer immunotherapy.

Keywords: Dermal fibroblast; Lymphoid tissue organizer cell; Lymphotoxin β receptor; Membrane-bound LTα(1)β(2); TNF-α receptor; Tertiary lymphoid organ.