Fig. 3

Each cell type present in the TME can contribute to the regulation of cancer progression and therapeutic response individually and thus several TME-directed therapies have been developed. The major strategies, which either have been FDA-approved or are currently being under clinical investigation, principally focus on the targeting of T-cells, DCs, TAMs, CAFs, ECM, and tumor vasculature; and thus, are indicated in the figure (black boxes) and referenced in the review. Targeting T-cells includes immune checkpoint inhibition, and T-cell therapies; targeting DCs comprises DC activation, DC recruitment, and DC vaccines; targeting TAMs consists of TAM depletion, and TAM re-education; targeting CAFs includes CAF depletion, inhibition of CAF activation, and CAF normalization; targeting ECM comprises increased ECM degradation, blockage of ECM synthesis, repurposing of drugs with antifibrotic properties, and targeting integrins or the downstream effector FAK; and targeting tumor vasculature consists of antiangiogenic therapies, and vessel normalization. DCs: Dendritic cells; TAMs: Tumor-associated macrophages; CAFs: Cancer-associated fibroblasts; ECM: Extracellular matrix; FAK: Focal adhesion kinase. This figure has been created with BioRender.com