CTGF: The remodeler of the tumor immune microenvironment (Review)

Abstract

The tumor immune microenvironment (TIME) is the key determinant of limited efficacy and acquired resistance to cancer immunotherapy across human malignancies. In this context, connective tissue growth factor (CTGF) has been implicated in multiple TIME-related processes, including tumor-cell phenotypic regulation, extracellular matrix (ECM) remodeling, immune-cell modulation, and cytokine-network alterations. Collectively, this suggests that CTGF may participate in coordinated crosstalk among structural, signaling, and immune components of the TIME. Empirical evidence supports roles for CTGF in selected tumor and stromal settings. However, its broader contribution to coordinated TIME remodeling remains partly inferential and requires further experimental validation. Where present, such coordinated effects may impair antitumor immune recognition and promote tumor-cell survival within specific tumor microenvironmental settings. The present review summarizes the core mechanisms of CTGF-mediated TIME remodeling and outlines the translational potential of CTGF-targeted combination immunotherapies and key research priorities to advance its clinical translation.