Not all cancerous tumors are created equal. Some tumors, called “hot” tumors, show signs of inflammation – that is, they are infiltrated with T cells that work to fight cancer. These tumors are easier to treat because immunotherapy drugs can then amplify the immune response.
“Cold” tumors, on the other hand, do not have an infiltration of T cells, which means the immune system does not intervene to help. With these tumors, immunotherapy is of little help.
It’s the latter type of tumor that researchers Michael Knitz and University of Colorado cancer center and radiation oncologist Sana Karam, MD, PhD, are discussing in new research published this week in the Journal for Cancer Immunotherapy. Working with mouse models in Karam’s specialty area of head and neck cancer, Knitz and Karam investigated the role of T cells in tumor treatment.
“What we found is that the cells that normally say to the T cell, ‘Hey, here’s a tumor – come and attack it,’ are silenced,” Karam says.
She and her team found that regulatory T cells (Treg), a type of specialized T cell that suppresses the immune response, essentially tell T cells to stop fighting cancer.
“Tregs normally serve as an important balance in a healthy immune system,” Knitz says. “They prevent autoimmune diseases and slow down T cells when needed. However, in many tumors, Tregs are either too numerous or too suppressive, which stops the T cell response.”
Researchers have found that using drugs that turn off Tregs can help boost the immune response in patients with cold tumors, much like radiation therapy which causes enough injury for immune cells known as dendritic cells. work to put regular T cells into combat mode.
But that’s only part of the story. T cells need to know what to attack. “You need the radiation to create wounds and bring in immune cells so the tumor can be recognized and targeted,” says Karam, also an associate professor of radiation oncology at the University of Colorado School of Medicine. “In this way, the dendritic cells trigger the immune system to produce a lot of T cells, like a vaccine does. These T cells then return to the tumor to kill the cancer cells. The pieces are already in place; They just need Activation of dendritic cells is a critical step in allowing radiation to warm these cold tumors. “
Importantly, Karam and his team, which includes post-doctoral fellow Thomas Bickett, have found that radiation must be administered in a specific way.
“A specific dosage is needed,” says Karam. “You have to pulse it. You can’t give a single dose. You have to give it back and combine it with suppressing elements – the Tregs – while keeping the antigen-presenting dendritic cells active and on board.”
Karam says the next step in her research is clinical trials which she hopes will ultimately change the treatment paradigm from surgery and weeks of chemotherapy and radiation therapy to just three sessions of radiation and immunotherapy. , then to surgery. She is driven to change the standard of care for cold tumors, she explains, because of the horrific effects they have on patients.
“These tumors look like those of patients who are heavy smokers,” she says. “They’re very destructive to bones and muscles, infiltrating the tongue, jaw, gum line, and lymph nodes. It’s horrible. We have very high failure rates with them, and treatment often involves it. tongue removal and weeks of radiation and chemotherapy, only for the patient’s failure. I have no doubts that we can do better for our patients. “