Teaching “Natural Born Killers” a Thing or Two

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Supporting our immune system: Allies in the fight against cancer

Our immune system is filled with powerful weaponry — T-cells, natural killer cells, macro­phages. It’s a complex world that has long perplexed medical professionals. So when a stealthy villain like cancer is able to slip past our defences, our response has generally been to overlook our internal artillery and go straight to the hired guns of chemotherapy, radiation and surgical scalpels.

But through decades of careful study, researchers are beginning to discern exactly how the various players of our immune system operate — and even how they can be co-opted by cancers to cross enemy lines. Based on these insights, we’re learning to empower our own body to fight off cancer from within.

One of the ways we’re doing this is by lending a hand to the immune system’s foot soldiers — the T-cells. These are white blood cells that are programmed to attack specific enemies, like foreign invaders or cancers. Immunology and Medical Biophysics Professor Pamela Ohashi has tracked the actions of T-cells for decades. She studied directly under U of T Professor Tak Wah Mak, who is famous in the scientific community for discovering the T-cell receptor in the 1980s.

Ohashi is especially interested in a T-cell known as a tumour-infiltrating lymphocyte, or TIL. These are T-cells sent in to attack cancer, only to get swallowed up and trapped within a rapidly growing tumour. Once this happens, TILs aren’t able to fight, or even to call for reinforcements. And it’s at this point where Ohashi and her team at Princess Margaret Cancer Centre’s Immune Therapy Program step in.

As part of an early phase trial based on promising research from the National Cancer Institute, they’re testing a technique called adoptive cell therapy in melanoma and ovarian cancer patients. Clinicians extract TILs from the patients’ tumours, expand them in large numbers in the lab and then reinject them into the patient, to attack remaining tumour cells en masse.

A crucial benefit of strengthening our own body to fight cancer is the potential for lasting protection — our immune system has a long memory. But it can still use some extra training. U of T Professors and Princess Margaret Cancer Centre researchers Marcus Butler and Naoto Hirano are focused on teaching our immune cells to recognize — and remember — specific cancers.

They use their deep understanding of cell signalling to develop artificial antigen-presenting cells that are able to prime the T-cells, helping them recognize and target specific cancers. They collaborate with Ohashi’s team to coach the T-cell army in vitro, before the cells are reinjected into patients.

As researchers learn more about our immune system, they’ve made some shocking discoveries — including evidence of our internal army working for the other side. For instance, Ohashi has observed how T-cells are less effective against certain tumours in the presence of natural killer cells. And Mak, who is director of Princess Margaret’s Campbell Family Institute for Breast Cancer Research, has observed a wall of macrophages that mysteriously forms around certain tumours, making it harder for helpful T-cells to get through.

Cancers have also been found to hijack our immune system by stepping on the brakes and shutting it down. As a response, U of T researchers are now using drugs known as “checkpoint inhibitors” to remove these brakes, in conjunction with adoptive cell therapy. The more we understand the dynamics at play, the more effectively we can join forces with — and even suppress insurrection among — our natural allies.

Learning to quell autoimmune diseases like multiple sclerosis

Autoimmune diseases are on the rise in Canada, and no one knows precisely why. We are also unsure of the best way to treat these often debilitating conditions, with many therapies targeting broad sections of the immune system instead of pinpointing a specific opponent. In the case of multiple sclerosis, we have no known cause and no cure.

Immunology Professor Jennifer Gommerman hopes to change that. She delves deep into the mechanisms behind autoimmune diseases, in an attempt to determine exactly how they develop. As one example, she recently discovered how a particular T-cell — a “helper” T-cell, no less — plays a central part in the formation of lymph node-like structures within the brain.

These “tertiary lymphoid tissues” have been associated with brain inflammation seen in progressive MS. While this is just one step in what is an incremental process of discovery, it’s through insights like this that we’re able to develop potential therapies. For example, might a treatment blocking the actions of this particular T-cell help counter the onset of MS? It may.

Only by understanding how and why our immune systems turn on us can we learn to quell the immuno-insurgency.