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 3,000+ scientific posters on ePosters
  • More than 4,500+ 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

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
NIH Awards Grants to Explore Vaccine Adjuvants
NIH awards six grants to explore how combination adjuvants improve vaccines.
Wednesday, April 06, 2016
Experimental Vaccine Protects Against Dengue Virus
An experimental dengue vaccine protected all the volunteers who received it from infection with a live dengue virus.
Wednesday, March 30, 2016
Experimental Ebola Antibody Protects Monkeys
Antibody isolated from Ebola survivor can advance to clinical trials.
Friday, February 26, 2016
Dengue Vaccine Enters Phase 3 Trial
Investigational vaccine to prevent ‘breakbone fever’ developed at NIH.
Friday, January 15, 2016
In Uveitis, Bacteria in Gut May Instruct Immune Cells to Attack the Eye
NIH scientists propose novel mechanism to explain autoimmune uveitis.
Wednesday, August 19, 2015
Novel Mechanism to Explain Autoimmune Uveitis Proposed
A new study on mice suggests that bacteria in the gut may provide a kind of training ground for immune cells to attack the eye.
Wednesday, August 19, 2015
HIV Control Through Treatment Durably Prevents Heterosexual Transmission of Virus
NIH-funded trial proves suppressive antiretroviral therapy for HIV-infected people effective in protecting uninfected partners.
Tuesday, July 21, 2015
Starting Antiretroviral Treatment Early Improves Outcomes for HIV-infected Individuals
NIH-funded trial results likely will impact global treatment guidelines.
Thursday, May 28, 2015
For Most Children with HIV and Low Immune Cell Count, Cells Rebound After Treatment
NIH-funded study finds T-cell level returns to normal with time.
Saturday, March 28, 2015
Strengthening the Immune System’s Fight Against Brain Cancer
NIH-funded research suggests novel way to improve vaccine efficacy in brain tumors.
Friday, March 20, 2015
Autoimmune Disease Super-Regulators Uncovered
Scientists discovered key genetic switches, called super-enhancers, involved in regulating the human immune system.
Tuesday, March 17, 2015
Scientific News
Gut Microbiomes Of Infants Have An Impact On Autoimmunity
Exposure to pathogens early in life is beneficial to the education and development of the human immune system.
Understanding Female HIV Transmission
Glowing virus maps points of entry through entire female reproductive tract for first time.
COPD Linked to Increased Bacterial Invasion
Persistent inflammation in COPD may result from a defect in the immune system that allows airway bacteria to invade deeper into the lung.
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.
Vaccinations Are More Effective When Administered In The Morning
Research from the University of Birmingham shows that influenza vaccinations have more protective responses when administered in the morning.
Secrets of a Deadly Virus Family Revealed
Scripps Research scientists uncover the glycoprotein structure of LCMV. The findings could guide development of treatments for Lassa fever.
Cytokine Triggers Immune Response at Expense of Blood Renewal
Research highlights promise of Anti-IL-1 drugs to treat chronic inflammatory disease.
Reduced Immune Response Causes Flu Deaths in Older Adults
Yale study suggests that immune response to flu causes death in older people, not the virus.
Exposure To Routine Viruses Makes Mice Better Test Subjects
Study shows that infections make mouse immune system act more like that in humans.
Immune Booster Tested in Advanced Merkel Cell Cancer
The immunotherapy drug produced durable responses in many patients.
SELECTBIO

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
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!