For cancer patients on immunotherapy, harmful gut bacteria might matter
more than helpful ones

Date:
February 28, 2022
Source:
Oregon State University
Summary:
Melanoma patients receiving therapy that helps their immune system
kill cancer cells respond to treatment differently depending on
the types of microbes in their gut, and new research suggests
the microorganisms hindering therapy have more influence than the
beneficial ones.



FULL STORY ========================================================================== Melanoma patients receiving therapy that helps their immune system kill
cancer cells respond to treatment differently depending on the types
of microbes in their gut, and new research suggests the microorganisms hindering therapy have more influence than the beneficial ones.


========================================================================== Findings by a collaboration that included researchers at Oregon State University, the National Cancer Institute, the Frederick National
Laboratory for Cancer Research and the University of Pittsburgh were
published today in Nature Medicine.

The research is a key step forward in the fight against multiple types
of cancer including melanoma, the most deadly form of skin cancer,
said Andrey Morgun of the OSU College of Pharmacy.

"Our findings shed new light on the highly complicated interaction
between the gut microbiome and cancer immunotherapy response and set a
course for future studies," he said.

Nationwide, melanoma is the fifth-most common cancer. Roughly 100,000 new melanoma cases will be diagnosed in the United States in the coming year,
and more than 7,000 of those patients are expected to die, according to
the American Cancer Society.

One of the most aggressive cancers, melanoma kills by metastasizing,
or spreading, to other organs such as the liver, lungs and brain.



==========================================================================
The new study involves a therapeutic technique called immune checkpoint blockade, often referred to by its initials of ICB, which has
revolutionized treatment of melanoma and cancer in general.

ICB therapy relies on inhibitor drugs that block proteins called
checkpoints that are produced by certain immune system cells -- T cells,
for example -- and also by some cancer cells.

Checkpoints help prevent immune responses from being too strong, but
sometimes that means keeping T cells from killing cancer cells. Thus,
when the checkpoints are blocked, T cells can do a better job of killing
cancer cells.

ICB has been a "game-changer" in cancer therapy, Morgun said, and
multiple studies have shown patients' gut microbes play a role in how
well a patient responds. The human gut microbiome is a complex community
of more than 10 trillion microbial cells representing roughly 1,000
different bacterial species.

Morgun and collaborators looked at data from multiple cohorts of melanoma patients receiving a type of ICB known as anti-programmed cell death
protein therapy, abbreviated to anti-PD-1 therapy.

Among other methods, they used a computer modeling technique, transkingdom network analysis, invented by Morgun and Natalia Shulzhenko of Oregon
State's Carlson College of Veterinary Medicine, to determine which
bacteria were associated with better or worse responses to the treatment.

"We established multiple microbiotypes and some of them were clearly
correlated with response to cancer immunotherapy," Morgun said. "Two
microbial signatures -- one comparatively heavy with Lachnospiraceae
species, the other comparatively heavy with Streptococcaceae species
-- were connected to favorable and unfavorable clinical response, respectively." The results also suggest that about a year after treatment begins the gut microbiota become a dominant factor in response to therapy,
and that the microbes that detract from therapy seem to play a bigger
role than the ones that enhance therapy, he added.

Amiran Dzutsev and Giorgio Trinchieri of the National Cancer Institute
and Hassane Zarour of the University of Pittsburgh are the corresponding authors on the study, which was supported by the National Institutes of
Health and the National Cancer Institute.

========================================================================== Story Source: Materials provided by Oregon_State_University. Original
written by Steve Lundeberg. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. John A. McCulloch, Diwakar Davar, Richard R. Rodrigues, Jonathan H.

Badger, Jennifer R. Fang, Alicia M. Cole, Ascharya K. Balaji,
Marie Vetizou, Stephanie M. Prescott, Miriam R. Fernandes, Raquel
G. F. Costa, Wuxing Yuan, Rosalba Salcedo, Erol Bahadiroglu,
Soumen Roy, Richelle N.

DeBlasio, Robert M. Morrison, Joe-Marc Chauvin, Quanquan Ding,
Bochra Zidi, Ava Lowin, Saranya Chakka, Wentao Gao, Ornella
Pagliano, Scarlett J. Ernst, Amy Rose, Nolan K. Newman,
Andrey Morgun, Hassane M. Zarour, Giorgio Trinchieri, Amiran
K. Dzutsev. Intestinal microbiota signatures of clinical response
and immune-related adverse events in melanoma patients treated with
anti-PD-1. Nature Medicine, 2022; DOI: 10.1038/ s41591-022-01698-2 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220228114333.htm

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