Researchers at the Wake Forest Institute for Regenerative Medicine (WFIRM) are using a tumor organoid system to examine the effect of bacterial-secreted metabolites on specialized immunotherapies (immune checkpoint blockade, a promising cancer treatment) development) to determine why some patients did not respond to treatment or developed resistance over time.
According to Cancer.gov, immune checkpoints are a normal part of the immune system, when proteins on the immune surface are involved Cells called T cells recognize and bind chaperone proteins on other cells, including tumor cells. When this happens, a “turn off” signal is sent to the T cells and prevents the immune system from destroying the cancer cells. Immunotherapy drugs work by preventing the binding and “turning off” the signal from being sent so that the T cells can do their job and kill the cancer cells.
Immune checkpoint blockade therapy has shown promising results in many cancer types, including unresectable advanced stages or metastases triple-negative breast cancer, and was recently approved as a promising treatment. However, clinical data show that approximately 40% of breast cancer patients do not respond to treatment.
“Immune checkpoint blockade immunotherapy is one of the latest and most promising developments in cancer treatment,” Atrium Health said Konstantinos I. Votanopoulos, MD, professor of surgery at Wake Forest Baptist Comprehensive Cancer Center and director of the Wake Forest Organoid Research Center. WFORCE), a joint venture between WFIRM and the Cancer Center. “It can have profound effects on patients who respond; however, the majority of patients either do not respond at all or become resistant to treatment over time, and we need to understand why.”
By integrating patient-derived immune system elements into tumor organoids, “we can now study the unique and complex interactions between the tumor, the immune system, and the microbiome. role,” adds Votanopoulos.
The human microbiome and its role in cancer, especially how it affects Response to therapies, such as immunotherapy, is an emerging area of research interest. The human microbiome is made up of microorganisms – viruses, bacteria and fungi – that exist in the body and support normal physiological functions. It is often described as an invisible system in the human body influenced by the genetics, geography, diet and lifestyle of the human host, and its understanding in the scientific community is still in its infancy.
In this study, recently published in Scientific Reports
, the research team created a new tumor organoid system containing important components of the immune system to study microbiome-related factors that influence immune checkpoint blockade responses. The team was able to show that some of these bacteria release factors (metabolites) that increase the viability of immune cells and alter gene expression, providing the system with a more complete immune response that improves therapeutic efficacy.
Dr. Shay Soker, who leads WFIRM’s organoid research team and is co-director of WFORCE, said results validate immune-enhanced tumors Organoid systems serve as physiological replicas, representing the in vivo state of the tumor microenvironment.
“Further understanding of the relationship between specific bacterial metabolites and overall response to immune checkpoint blockade can be used to drive positive potential outcomes,” Soker said. “Procedures such as fecal transfer or dietary modification can also be effective in inducing a more therapeutically beneficial microbiome.”
Soker and Votanopoulos say More data are needed to determine the relationship between these receptors, bacterial metabolites and therapeutic response. Further use of this model with patient-derived cells will help demonstrate the full impact of these factors, they add.
“These results suggest that further development of this model will ultimately be important for the design and analysis of future anticancer treatment trials clinical tool,” said WFIRM Director Anthony Atala, MD. “Our goal is to integrate the immune-enhancing tumor organoid platform into the treatment decision-making process to better treat patients.”
Additional co-authors include: Ethan Shelkey, David Oommen, Elizabeth R. Stirling, David R. Soto-Pantoja, Katherine L Cook and Yong Lu. The authors declare no competing interests.
Further information: Ethan Shelkey et al., Immunoreactive Cancer Organoid Models for Assessing the Microbiome Implications for Cancer Immunotherapy, Scientific Reports (2022). DOI: 10.1038/s41598-022-13930-7
Courtesy of Atrium Healthy Wake Forest Baptist Church
Citation : Researchers create cancer-specific organoid system to study the effect of bacteria on immunotherapy (29 July 2022 date), retrieved August 27, 2022, from https://medicalxpress.com/news/2022-07-specific-cancer-organoid-bacterial-effects.html
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