Study brings hope for patients with solid tumors
Our bodies have an immune system to prevent or fight against illnesses and infections. The immune system is critical for us to keep health. Individuals with a weakened immune system are more susceptible to illnesses and infections compared with those with a normal immune system. But, in many cases, even if the immune system is fully functioning, cancer occurs. Scientific research has demonstrated that tumors may hijack some types of immune cells, such as tumour-associated macrophages (TAMs) and regulatory T cells (Tregs), to create a microenviroment that favors tumor growth and suppresses immune attacks. Previous studies have shown that TAMs and Tregs can promote tumor progression by limiting antitumor immunity.
So, preventing tumors from hijacking TAMs or Tregs represent a therapeutic strategy against cancer. Animal experiments have shown that inhibition of TAM recruitment through inhibition of CSF1
is capable of decreasing tumor growth. However, this strategy doesn't work well in humans, and little is known about how TAMs contribute to tumor development. Studies have shown that inhibition of Tregs through inactivation of PI3K delta could fight many tumors, and currently there is already a PI3K delta inhibitor used in leukaemia treatment. However, it remains a mystery whether PI3K delta inhibitors could apply to solid tumors.
To conclude, by hijacking TAMs and Tregs, tumors seem to get two 'arms' to escape the anti-tumor attacks of the immune system. Therapies that only target only one of the 'arms' may be not effective enough. Now, a new study has shown that targeting TAMs and Tregs at the same time could be a potential way to treat tumor.
In the study, researchers from Babraham Institute and Karus Therapeutics Ltd. used a mouse model of colorectal cancer to investigate the influence of TAMs and Tregs on tumor growth. They found that when the tumor-promoting effect of TAMs was reduced, the tumor-promoting effect of Tregs was increased, and vice versa. In a word, TAMs and Tregs constitute a compensatory network that supports the immunosuppressive tumor microenvironment. Furthermore, when the researchers inhibited both TAMs and Tregs, tumor growth was substantially suppressed.
These results suggest inhibition of both TAMs and Tregs as a way to treat solid tumors like colorectal cancer.
Findings of the study have been summarized in a paper titled "Compensation between CSF1R+ macrophages and Foxp3+ Treg cells drives resistance to tumor immunotherapy," appearing in JCI Insight.