Corporate Banner
Satellite Banner
Immunology
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Study Finds Gut Microorganisms May Determine Cancer Treatment Outcome

Published: Monday, November 25, 2013
Last Updated: Monday, November 25, 2013
Bookmark and Share
An intact population of microorganisms that derive food and benefit from other organisms living in the intestine is required for optimal response to cancer therapy.

NCI scientists found that tumors of germ-free mice (mice completely lacking these microorganisms), or mice treated with antibiotics to deplete the gut of bacteria, were largely impaired in their ability to respond to immunotherapy that slows cancer growth and prolongs survival. The mice were also impaired in their ability to respond to mainstay chemotherapy drugs such as oxaliplatin and cisplatin. These findings in mice may underscore the importance of microorganisms in optimal cancer treatment outcomes in humans. The study, led by Romina Goldszmid, Ph.D., staff scientist, NCI, and Giorgio Trinchieri, M.D., director of the Cancer and Inflammation Program, Center for Cancer Research, NCI, appeared Nov. 22, 2013, in Science.

Gut commensal microbiota are microorganisms that live in the gut and thrive but do not affect their host, in this case laboratory mice. Humans also harbor gut commensal microbiota that can influence local and body-wide inflammation as well as modify the tumor microenvironment, which consists of cells, signaling molecules and mechanisms that may support tumor growth and also cause drug resistance.

To study the importance of commensal bacteria, the scientists used mice raised in sterile conditions from birth so they did not harbor any bacteria, or alternatively, conventionally raised mice that received a potent antibiotic cocktail that is known to decrease bacteria by more than 10,000–fold.  The mice received these antibiotics in their drinking water, starting three weeks prior to tumor inoculation. They continued to receive doses of the antibiotic cocktail throughout the experiment.

To analyze tumors at comparable stages of progression, lymphoma, colon, and melanoma cancers that could be transplanted were selected, based on their susceptibility to therapeutic drugs. Cancer cells from these tumors were then injected under the skin of the mice, where they formed tumors that grew to reach a diameter of one-fifth of an inch or more. The tumors were then treated with an immunotherapy that included CpG-oligonucleotides, which stimulated the immune system, or with the chemotherapy drugs oxaliplatin and cisplatin, which attacked the tumors.

Germ-free mice, or mice that received the antibiotic cocktail, responded poorly to drug therapy for their tumors. This resulted in a lower production of cytokines (proteins secreted by lymph cells that affects cellular activity and controls inflammation) as well as lower tumor death therefore demonstrating that optimal responses to cancer therapy required an intact commensal microbiota.

In an independent co-submitted study that will appear in the same issue of Science, Laurence Zitvogel, M.D., Ph.D., Gustave Roussy Institute, Paris, and colleagues showed that a different type of chemotherapy drug, cyclophosphamide, altered the composition of the intestinal microbiota and damaged the intestinal wall, thereby affecting optimal anti-tumor immune response and the therapeutic effectiveness of cyclophosphamide.

“The use of antibiotics should be considered as an important element affecting microbiota composition. It has been demonstrated, and our present study has confirmed, that after antibiotic treatment the bacterial composition in the gut never returns to its initial composition,” said Trinchieri. “Thus, our findings raise the possibility that the frequent use of antibiotics during a patient’s lifetime or to treat infections related to cancer and its side-effects may affect the success of anti-cancer therapy.”

In next steps, Goldszmid and Trinchieri will work in mice to fully characterize the molecular signaling by which the bacteria in the gut can actually send messages to distant organs or tumors and change the type and level of inflammation present in those organs. They also plan to characterize, in humans, the role of gut bacteria on the bodies’ inflammatory response and tumor response to therapy. Additionally, the researchers plan to design clinical studies by giving antibiotics to healthy volunteers to study their effect on the molecular mechanisms regulating inflammation.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,500+ scientific posters on ePosters
  • More than 5,000+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Researchers Find a Gap in the Brain’s Firewall Against Parkinson’s Disease
Researchers at NIH have found mouse study that identified a key player in the progression of the disorder.
Saturday, October 01, 2016
Oxygen Can Impair Cancer Immunotherapy
Researchers have identified a mechanism within the lungs where anticancer immune resposnse is inhibited.
Friday, August 26, 2016
New Inflammatory Disease Discovered
NIH researchers have discovered a rare and potentially deadly disease - otulipenia - the mostly affects children.
Tuesday, August 23, 2016
Oral Immunotherapy Is Safe, Effective Treatment for Peanut-Allergic Preschoolers
Study demonstrates the potential of peanut OIT to suppress allergic immune responses to peanut.
Friday, August 12, 2016
Mutations Linked to Immunotherapy Resistance
Researchers uncover mutations in tumors of three patients with advanced melanoma that allowed the tumors to become resistant to the immune checkpoint inhibitor pembrolizumab (Keytruda®).
Tuesday, August 09, 2016
Zika Vaccine Candidates Show Promise
Two experimental vaccines have shown promise against a major viral strain responsible for the Brazilian Zika outbreak.
Friday, July 29, 2016
Targeting Autoimmunity
Researchers have developed a strategy to treat a rare autoimmune disease which could lead to treatments of other autoimmune diseases.
Wednesday, July 27, 2016
NIH Investment Into HIV Research Expands
Funding has been awarded to six research teams to lead collaborative investigations worldwide toward an HIV cure.
Thursday, July 14, 2016
Drug Might Help Treat Sepsis
A DNA enzyme called Top1 plays a key role in turning on genes that cause inflammation in mouse and human cells in response to pathogens. A drug blocking this enzyme rescued mice from lethal inflammatory responses, suggesting a potential treatment for sepsis.
Wednesday, May 18, 2016
Large-scale HIV Vaccine Trial to Launch in South Africa
NIH-funded study will test safety, efficacy of vaccine regimen.
Wednesday, May 18, 2016
New HIV Vaccine Target Discovered
NIH-Led team have discovered a new vaccine target site on HIV.
Tuesday, May 17, 2016
Finding Factors That Protect Against Flu
A clinical trial examining the body’s response to seasonal flu suggests new approaches for evaluating the effectiveness of seasonal flu vaccines.
Wednesday, April 27, 2016
Factors Influencing Influenza Vaccine Effectiveness Uncovered
The long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited, new research suggests.
Thursday, April 21, 2016
Study Finds Factors That May Influence Influenza Vaccine Effectiveness
Researchers at NIH have suggested that the long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited.
Wednesday, April 20, 2016
Submissions Open for the Cancer Moonshot Program
NCI opens online platform to submit ideas about research for Cancer Moonshot.
Tuesday, April 19, 2016
Scientific News
Point of Care Diagnostics - A Cautious Revolution
Advances in molecular biology, coupled with the miniaturization and improved sensitivity of assays and devices in general, have enabled a new wave of point-of-care (POC) or “bedside” diagnostics.
Researchers Find a Gap in the Brain’s Firewall Against Parkinson’s Disease
Researchers at NIH have found mouse study that identified a key player in the progression of the disorder.
‘Cellbots’ Chase Down Cancer, Deliver Drugs Directly to Tumors
Programmable T cells shown to be versatile, precise, and powerful in lab studies.
Faecal Bacteria Linked to Body Fat
Researchers at King’s College London have found a new link between the diversity of bacteria in human poo – known as the human faecal microbiome - and levels of abdominal body fat.
Anti-Inflammatory Drugs Could Strengthen Airway Immunity
Mold toxins can weaken the airways' clearing mechanisms and immunity, but PKC inhibitors showed promise as a treatment.
Antibodies Paving the Way to HIV Vaccine
Researchers uncover factors responsible for the formation of broadly neutralizing HIV antibodies in humans.
Vaccine Against Common Cold Achievable
Researchers suggest that a vaccine against rhinoviruses is possible using variant virus vaccines.
Treating Sepsis with Marine Mitochondria
Mitochondrial alternative oxidase from a marine animal combats bacterial sepsis.
Iron Nanoparticles Make Immune Cells Attack Cancer
Researchers accidentally discover that nanoparticles invented for anemia treatment can trigger the immune system’s ability to destroy tumor cells.
Uncovering Cancer’s ‘Invisibility Cloak’
Researchers discover cancer cell mechanism to become invisible to the body's immune system.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,000+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!