Exposing tumors to bacteria converts immune cells into cancer killers

According to researchers from UNSW Sydney and the Garvan Institute of Medical Research, the introduction of bacteria into the microenvironment of a tumor creates a state of acute inflammation that prompts the immune system’s primary response cells to attack rather than attack. to protect a tumour.

At the first signs of bacterial infection, the first cells on the scene are white blood cells called neutrophils, which play an important role in defending against infection.

Although they generally protect against disease, they are known to promote tumor growth. High levels of them in the blood are generally associated with poorer cancer outcomes, in part because they produce molecules that protect the tumor by suppressing other parts of the immune system.

The team of scientists found that injecting inactivated samples of the microbe Staphylococcus aureus into the tumor microenvironment – the area surrounding the tumor – reverses the protective function of neutrophils.

The research, published in the journal Research against cancer, was led by Associate Professor Tatyana Chtanova in the UNSW School of Biotechnology and Biomolecular Sciences and Head of the Innate and Tumor Immunology Laboratory at Garvan. A/Prof Chtanova says these findings have helped advance our understanding of acute inflammation to advance microbial cancer therapy.

“In our study, we sought to develop new immunotherapies that use different modes of action that could complement and improve existing immunotherapies,” explains A/Prof Chtanova.

“We show how acute inflammation can be harnessed to achieve continued anti-tumor function in immune cells. We also show how microbial therapy can be successfully combined with an existing type of therapy, known as checkpoint inhibitor therapy, to amplify anti-cancer capabilities.

Explore new ways to trigger the immune system to fight cancer

Working on a range of animal cancer models, including Lewis lung carcinoma, triple-negative breast cancer, melanoma and pancreatic cancer, the presence of bacteria stimulated neutrophils to destroy tumors.

“Using the immune system to fight cancer has been one of the biggest breakthroughs in cancer treatment in the last two decades, but currently immunotherapy to improve the function of T cells (another type important number of white blood cells) does not work for all types of cancer,” explains Professor a/chtanova.

“We decided to use a different type of immunotherapy that targets neutrophils, to understand how the generation of acute inflammation in the immunosuppressive tumor microenvironment affects outcomes.”

The team studied the tumors in real time using a unique imaging method called intravital imaging.

“Since bacteria attack is the reason neutrophils exist, we had a good idea that introducing bacteria would bring neutrophils to the site and activate them. We’ve found that’s very effective in getting them to kill tumors, to chew through their matrix,” she says.

The study also revealed that upon exposure to bacteria, neutrophils begin to secrete molecules that will attract fighting T cells as reinforcement.

“We have shown that microbial therapy is an effective booster for checkpoint inhibitor therapy. We hope that this synergistic effect will ultimately lead to better treatments to improve outcomes for patients with advanced or previously incurable cancers,” says study first author Dr. Andrew Yam, clinical medical oncologist at Kinghorn Cancer Center and PhD student at Garvan.

This study focused on primary tumors, the first tumor in the body. “So far, we have shown that our microbial therapy can inhibit the growth of primary tumors and can also protect against tumor recurrence, which is a major clinical challenge,” says A/Prof Chtanova. “This suggests that our microbial therapy achieves not only short-term and localized, but also long-lasting and systemic anti-tumor immunity.

“Our next step is to extend these findings to develop a pathway for treating cancers that have metastasized to different locations.”

Leave a Comment