Results from a study spearhead by researchers at the Vall d´Hebron Institute of Oncology (VHIO), show that the blockade of the multi-functional cytokine LIF induces tumor-infiltrating T Cells to hone in on and eliminate cancer.
novel agent MSC-1 inhibits LIF and has now been shown to have a dual mechanism of action. First, in tumors expressing high levels of LIF, this protein promotes the proliferation of cancer stem cells. LIF blockade eliminates these tumor-initiating stem cells, putting the brakes on metastatic cell spread and cancer recurrence.
Additionally, elevated LIF expression disables the anti-tumor alarm system and stops the immune system from thwarting cancer's plans. Blocking LIF reactivates the alarm to call an anti-tumoral immune response.
Pioneer of previous LIF studies, Joan Seoane and his team were the first to establish a link between this multi-functional protein and cancer as well as show that LIF blockade eliminates cancer stem cells and prevents disease progression and recurrence. In this present paper, they have now revealed its implication in the immune system's anti-cancer response.
When foreign bodies or alterations in healthy cells are detected, a biological alarm alerts the immune system to act against these 'dealers' of damage. "We have discovered that LIF silences this alarm which enables cancer to dodge the immune system's innate response. It´s just like a bank robber deactivating an alarm to escape detection by the police," explains Joan Seoane.
More specifically, the researchers have shown that LIF inhibits the CXCL9 gene, which acts as a signal to lure immune system T cells. LIF blockade induces these immune system soldiers to invade, attack and destroy tumors. "We have observed that LIF inhibition in tumors expressing high levels of this protein reactivates the signal to T cells to target and destroy cancer," says Joan.
This study also shows that combining LIF inhibition with anti-PD1 therapy powerful blows against cancer. "Once the T cells infiltrate the tumors, they are activated by anti-PD1 immunotherapy. In animal models the pairing of both agents not only halted tumor growth but also, in some cases, made tumors disappear. In these cases, the immune memory is activated and the system 'remembers' the tumor and that particular does not reappear even when more tumor cells emerge,"
Immunotherapy (general) - Interesting NY Times Article.
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