Table 2 Main target sites of immunotherapy in tumor-associated macrophage regulation
From: Dual roles and therapeutic targeting of tumor-associated macrophages in tumor microenvironments
Pathways | Target | Drugs/Inhibitors | Change in TAMs | Refs. |
|---|---|---|---|---|
Termination of Macrophage Recruitment | ||||
CCL2/CCR2 | CCR2 | RDC018 | RDC018 act as the CCR2 antagonist and reduces macrophage infiltration | |
CCX872 | Lower the ETV4-induced TAMs recruitment and infiltration, which further inhibits the HCC metastasis | |||
sc-202525 (CCR2 antagonist) | Reduced TAM infiltration | |||
NF-κB/CCL2 | CCL2 | TGP | TGP reduces the release and recruitment of inflammatory factors, which suppress the infiltration of TAMs in TME | |
IGF-1R-IRS and JAK-STAT3 | IGF-1R and STAT3 | NT157 | Short-term: No obvious change; Long-term: NT157 inhibited the production of TAM inducers, indicating a long-term inhibiting effect of TAM recruitment | |
CSF-1/CSF-1R | CSF-1R | BLZ945 | Using a CSF-1R tyrosine kinase inhibitor (BLZ945) can counteract the improvement in total TAM content response to radiotherapy | |
Release of Immunostimulatory Capacity | ||||
CCL2/CCR2 | CCL2 | LINC00330 (intergenic noncoding RNA) | The expression of LINC00330 is negatively linked to M2-type TAMs and positively linked to M1 TAMs. Reprogram TAMs polarization toward the M1 state. | |
NF-κB/CCL2 | CCL2 | TGP | TGP reduces the release of CCL2, which restrains TAM polarization toward the M2 state | |
CSF-1/CSF-1R | CSF-1R | M2pep-Modified Cyclodextrin-siRNA | Downregulation of CSF-1R achieved by siRNA reprogramming M2-type TAM into M1-type TAM | |
CSF-1R-siRNA | Increase in M1 cytokine production and reduction in M2, which represent a repolarization of M2-type TAM into M1-type | |||
PLX3397 (CSF-1R inhibitor) | Impede M2-type TAM polarization and reprogrammed M2-type TAMs into M1-type | |||
OX40/OX40L | OX40 | OX40L M1-exos | Signature receptor CD86 of M1-type TAMs is upregulated, while CD206 for M2-type TAMs is downregulated. | |
OXCT1-Arg1 | OXCT1 | OXCT1 Knockout/Pimozide (OXCT1 inhibitor) | OXCT1 enriched in the M2-type TAMs and OXCT1 deficiency can induce the reprogramming of TAMs into tumor-suppressive type M1 | |
Removal of TAMs | ||||
CSF-1/CSF-1R | CSF-1R | BLZ945 | Removal of TAMs in tissue specificity manner in cervical cancer and repolarization TAMs in microglia | |
PLX3397 | Depletion of TAMs and alter TAM-related gene expression toward M1 type | |||
