Researchers create specific cancer organoid system to study bacterial effects on immunotherapy

WFIRM’s tumor-on-a-chip system is used to test drug therapies. Credit: WFIRM

Wake Forest Institute for Regenerative Medicine (WFIRM) researchers are using the tumor system to investigate the effect of metabolites secreted by bacteria on a specific immune system – blocking immune checkpoints, developing cancer drugs – to determine why causing some patients to not respond or develop resistance to medication over time.

According to, immunological research sites it’s part of my culture immune system which occur when proteins on the surface of immune cells, called T cells, identify and bind to proteins on other cells, including cancer cells. When this happens, a “kill” signal is sent to the T cells and prevents the immune system from destroying cancer cells. Antibiotics work to block the binding and “off” signals from being sent so that T cells can do their job and kill cancer cells.

Immune checkpoint blockade therapy has shown promising results in many types of cancer, including unresectable advanced or triple-negative breast cancer and has recently been approved as a treatment for interesting. However, clinical information showed that about 40 percent of breast cancer patients do not respond to therapy.

“Immune checkpoint blockade immunotherapy is one of the newest and most promising advances in cancer treatment,” said Konstantinos I. Votanopoulos, M.D., Ph.D., professor of surgery at Atrium Health Wake Forest Baptist Comprehensive Medical Center. Cancer Center and Wake director. Forest Organoid Research Center (WFORCE), a collaboration between WFIRM and the cancer center. “It can show a profound effect in patients who respond; however, many patients show either a lack of response or develop resistance to the drug over time and we need to understand why.”

By connecting the components of the immune system from the patient to the microbiome, “we can now study the unique and complex interactions between the virus, the immune system and the microbiome,” Votanopoulos said.

The human microbiome and its role in cancer, and particularly how it affects response to therapies such as immunotherapy, is an emerging area of ​​research interest. The human microbiome consists of microorganisms – bacteria, viruses and fungi – that live in the body and work to support optimal physiological function. It is often described as an invisible process in the human body that affects the human body, climate, diet and lifestyle, and the scientific community’s understanding of it is still in its infancy.

In this study, recently published a Scientific Reports, the research team has developed a new microbiome system that incorporates key components of the immune system to study microbiome-related factors that influence the immune barrier response. The team was able to show that some of these metabolites improved the health of the cells and changed the expression of the cells in the primary system for a complete immune response, thus increasing the amount of the drug.

Shay Soker, Ph.D., who leads the organoid research group at WFIRM and is the executive director of WFORCE, said that the results confirm the efficiency of the organoid system as a physiological replica that represents in vivo microbial environment.

“Further understanding of the relationship between specific pathogens and the overall response to blocking immune checkpoints can be used to push for better outcomes,” said Soker. “Procedures such as fecal transfer or dietary modification can create an improved microbiome suitable for treatment.”

Soker and Votanopoulos say more data is needed to determine the relationship between these receptors, the cells, and the therapeutic response. Continued use of this product with patient-derived cells will help demonstrate the full effect of these factors, they added.

“These results indicate that the continued development of this model will be an important clinical tool in the planning and analysis of future trials for the treatment of cancer,” said WFIRM Director Anthony Atala, MD. “Our goal is to integrate the organoid platform into the decision-making process for patient care.”

Additional authors include: Ethan Shelkey, David Oommen, Elizabeth R. Stirling, David R. Soto-Pantoja, Katherine L Cook and Yong Lu. The authors disclose no competing interests.

Personalized immunotherapy response studied in cancer models-on-a-chip

Additional information:
Ethan Shelkey ​​​​et al, Immuno-reactive cancer organoid model to assess the effect of the microbiome on cancer immunotherapy, Scientific Reports (2022). DOI: 10.1038/s41598-022-13930-7

Atrium Health Wake Forest Baptist was created

hint: Researchers create cancer-specific organoid system to study effect of cancer cells on immunotherapy (2022, July 29) retrieved 29 July 2022 from -bacterial-effects.html

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