Related Experiment Video
Updated: Sep 27, 2026

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
Published on: November 28, 2019
Tumor-derived cytokines dysregulate macrophage interferon-gamma responsiveness and interferon regulatory factor-8
David W Mullins1, Ryan S Martins, Klaus D Elgert
1Department of Biology, Microbiology and Immunology Section, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061-0406, USA. dmullins@virginia.edu
Abstract:
Tumors can evade immune responses through suppressor signals that dysregulate host effector cell function. In this study we demonstrate that tumor-derived suppressor molecules impede host antitumor immune activity through dysregulation of multiple macrophage (Mphi) pathways, including suppressed production of cytotoxic and immunostimulatory agents and impaired expression of the interferon regulatory factor-8 (IRF-8) protein, a critical transducer of interferon-gamma-mediated activation pathways. The tumor-derived immunosuppressive cytokines interleukin-10 and transforming growth factor-beta(1) constrain IRF-8 production by normal Mphis, regardless of priming, and IRF-8 is also dysregulated in primary Mphis from tumor-burdened hosts. Collectively, these data describe a new mechanism by which tumors disrupt immune function and suggest that abrogation of tumor-derived immunoregulatory factors in situ can restore immune function and enhance antitumor efficacy.
Related Concept Videos
The Tumor Microenvironment
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
TGF - β Signaling Pathway
