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Discovery: New Immunotherapy for Malignant Tumors

February 24, 2019 - OBJECTIVE: As one of the most important mediators of cancer-related inflammation and drug resistance in immunotherapy, tumor-associated macrophages (TAM) have become an important target of anti-cancer immunotherapy drugs. However, the efficacy of TAM clearance strategy in clinical research is not optimistic.

Another strategy that has emerged in recent years is to explore the plasticity of macrophages and to re-educate TAM, which promotes tumor phenotype, into a phenotype of immune stimulation, thereby activating the body's anti-tumor immune response.

Experimental design: Researchers from Turku University and other institutions in Finland have recently explored the effects of macrophage scavenger receptor Clever-1 on the growth of tumors in a variety of mouse tumor models, which are characterized by inflammation or non-inflammation, through conditional knockout, bone marrow chimerism and cell depletion experiments. In addition, the researchers tested the efficacy of Clever-1 inhibition as an immunotherapy or in combination with anti-PD-1 inhibitors.

Results: Clever-1 gene defect in macrophages significantly inhibited the growth of solid tumors. This effect is mediated by macrophages that become immunoregulatory phenotypes in the absence of Clever-1. These macrophages reverse the tumor immunosuppressive microenvironment into an inflammatory environment and activate endogenous anti-tumor CD8 positive T cells. Similar therapeutic effects can be achieved by immunotherapeutic inhibition of Clever-1. It is noteworthy that these effects are comparable to those of anti-PD-1 inhibitors. In addition, the combination of anti-Clever-1 and anti-PD-1 therapy can produce synergistic effects in malignant non-responsive advanced tumors and inhibit the growth of tumors.

CONCLUSION: This study demonstrates the importance of macrophages in mediating anti-tumor immune response and provides evidence that inhibiting Clever-1 may be a new anti-cancer immunotherapy strategy.
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