New mechanism may help predict and improve macrophage-targeted cancer immunotherapy
Immunotherapy that targets tumor-associated macrophages, a type of immune cell in the tumor microenvironment, works only if the cells have a functional system of molecules that enables them to respond to the treatment. This is shown in a new study from Karolinska Institutet, published in the journal Nature Communications. The findings may help identify which tumors could respond to the treatment…
A new study from Karolinska Institutet suggests that a mechanism involving functional endosomal Toll-like receptors, particularly TLR9, could help predict and enhance macrophage-targeted cancer immunotherapy. The researchers found that the success of immunotherapy targeting tumor-associated macrophages depends on these receptors enabling the macrophages to respond to the treatment.
Without functional TLR9, macrophages remain in an immunosuppressive state and the treatment is ineffective, as observed in mouse models. When TLR9 activation is combined with the immunotherapy, the treatment effect is enhanced, indicating that TLR9 could potentially boost the response and make the treatment more effective. Furthermore, analysis of human tumor samples showed associations between the expression of the treatment target MARCO and TLR9, suggesting that these mechanisms may also be relevant in humans.
The study, conducted in collaboration with the University of Toronto, Rockefeller University, and university hospital clinical departments, used mouse models and aims to develop and test new treatment strategies, including combinations of immunotherapies, to improve effectiveness in patients with currently difficult-to-treat tumors.
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