Targeting the Barriers Driving Immune Exclusion

Immune exclusion refers to the phenomenon in which immune cells are restricted to the peritumoral stroma. This phenomenon arises from complex interactions within the tumor microenvironment (TME) that limit immune cell infiltration. Consequently, immune exclusion represents a major barrier to effective antitumor immunity and a key obstacle to the success of immunotherapy. The principal components of the TME that orchestrate immune exclusion are (i) the tumor vasculature, (ii) the extracellular matrix (ECM), and (iii) stromal cells and their chemokine-mediated signaling. Understanding immune exclusion is critical for designing therapies that enhance the efficacy of immunotherapy and improve clinical outcomes. This review synthesizes current knowledge of the molecular and cellular mechanisms underlying immune exclusion and discusses emerging therapeutic strategies aimed at overcoming this phenomenon.