FIGURE 2.

Current onco‐therapeutic strategies utilizing properties of primary tumor microenvironment (TME) cellular components. (A) Onco‐therapeutic strategies utilizing tumor‐infiltrating lymphocyte (TIL) properties largely rely on blocking immune checkpoints. (B) Onco‐therapeutic strategies targeting tumor‐associated macrophages (TAMs) either eradicate TAMs or repolarize TAMs from the M2 to the M1 state. (C) Onco‐therapeutic strategies targeting cancer‐associated fibroblasts (CAFs) mainly target myofibroblastic CAFs (myCAFs) and inflammatory CAFs (iCAFs). As myCAFs are featured by ‘high α‐SMA and low IL6’ and are activated by TGFβ/SMAD signaling, therapeutics against myCAFs are designed to target the TGFβ/SMAD axis. As iCAFs are characterized by ‘low α‐SMA and high IL6’ and are activated by JAK/STAT signaling, therapeutics killing these cells are designed to target the JAK/STAT axis. Therapeutics have also been proposed to target miRNAs in CAF‐derived exosomes. (D) Onco‐therapeutic strategies targeting mesenchymal stem cells (MSCs) can be either targeting MSCs or their derived exosomes. MSCs of different origins and their derived exosomes can be used for delivering drugs, including chemotherapies, nano‐based chemotherapies, nanoparticles, and oncolytic viruses. MSC‐derived exosomes can also be genetically modified to deliver cytokines, tumor suppressors, or miRNAs to tumors or the TME towards desirable therapeutic outcome.