Susanna Fletcher Greer: From weeds to warriors – how cancer’s helpers are becoming its worst enemy
Susanna Fletcher Greer, Chief Scientific Officer of the V Foundation, shared a post on LinkedIn:
“From weeds to warriors: how cancer’s helpers are becoming its worst enemy.
Think of a garden in early spring. You’ve pulled out the obvious weeds, planted seeds, and you’re waiting for those flowers to bloom. But something’s still off, your flowers won’t grow because the soil is full of pests hiding beneath the surface, quietly ruining your hard work. That’s kind of what’s happening in some cancer immunotherapy treatments right now.
Today’s most powerful cancer immunotherapies, called immune checkpoint inhibitors, are like pulling out the obvious weeds. They’ve changed lives, especially in cancers like melanoma, but they don’t work for everyone.
Some tumors stay stubborn and resistant. Why? Because of sneaky cells hiding in the ‘soil’ of the tumor, like an old fungus or bacteria we can’t easily ‘see’, and these are the cells that help cancer survive.
These cells are called macrophages, they are your body’s cleanup crew that, in a healthy environment, eat up dead cells and help with healing. But in cancer, some of them get ‘reprogrammed’ to do the opposite.
Instead of helping your immune system fight the tumor, they actually protect it, kind of like garden pests like bacteria that help the weeds take over.
This V Foundation-funded study focuses on a special ‘badge’ that many of these macrophages wear, called MARCO. It’s a protein, or a receptor, that tells them what to pick up and respond to.
The V Foundation grantee Dr. James Mule’ at the Moffitt Cancer Center found that by blocking MARCO, and not killing the macrophages, but changing what they do, they could flip these cancer-helping cells back into cancer-fighting ones. Kind of like turning pests into pollinators.
When Dr. Mule and team combined this MARCO-blocking strategy with an existing immune therapy (anti-CTLA-4, which helps immune cells wake up and attack cancer), the results were striking. The immune system flooded the tumor with fresh reinforcements: mature cells that could sound the alarm and rally more defenders.
This new combination approach could help patients whose tumors don’t respond well to current immunotherapies, especially those with so-called ‘cold’ tumors, where the immune system barely shows up. It could also give a big advantage to newer therapies like CAR-T cells, helping them find and fight cancer more effectively.
Instead of just yanking out the ‘weeds’, this research helps us fertilize the immune system’s soil, making it more welcoming to immune cells and less friendly to cancer.
And in this season, what I often think of as the springtime of cancer research, THIS could be one way we start turning stubborn patches into blooming fields of possibility. Great work Dr. Mule and team; I love a good garden and gardener.
Find the Mule lab here and read this awesome paper here.”
Authors: Hidenori Takahashi, Patricio Perez-Villarroel, Rana Falahat, James Mulé.
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