SPRING 2022 | THE SCIENTIST 45MICRONOMAtion, applied for intellectual property to cover the approach
and began the process of founding Micronoma. The company
incorporated in the summer of 2019 and officially launched in
August 2020 (enlisting Straussman and later Wargo to its scien-
tific advisory board and giving them stock options). For its first
product, Micronoma is focusing on a test for lung cancer, and
collaborations are underway to develop diagnostics for other
cancer types, says Miller-Montgomery, now CEO and president
of the company. “The goal is to put this in the hands of clini-
cians and in the hands of patients.” In December, Sepich-Poore
defended his dissertation and officially joined Micronoma full-
time as its chief analytics officer.
Already, other labs have started to generate findings that support
the idea that microbes could aid in cancer diagnosis. Last summer,
for example, researchers reported that they’d identified microbial
DNA signatures in the blood of melanoma patients that distin-
guished them from healthy controls.^6 “We see that as a very impor-
tant confirmation,” says Knight. It’s especially exciting because mel-
anoma was the cancer type for which their diagnostic algorithms
performed the worst, he adds—not terrible, but not as good as the
rest. “We’re very encouraged that even in that worst case another
group was independently able to see highly significant results.”
Microbial signatures may also contain prognostic information,
potentially helping to predict treatment response. In Straussman’s
2020 study, for example, melanoma patients in the data set had
different microbial signatures in their tumors if they did or did
not respond to immunotherapy. “You can find bacteria that are
enriched in responders or nonresponders,” Straussman says. And
less than a year earlier, MD Anderson physician-scientist Floren-
cia McAllister, along with Wargo and other colleagues, found that
the tumor microbiome could indicate whether patients with pan-
creatic cancer had lived longer than five years following diagnosis
with the disease.^7 “The heterogeneity of microbes in the tumor was
higher in the patients that live longer,” says McAllister, who has
a patent pending based on the work. The million-dollar question
now is what effect bacteria and possibly other microbes have on
tumor development, progression, and response to treatment. “It’sone thing to descriptively say these bacteria are present in these
tumor types,” says Straussman. “We need to learn more and more
about how these bacteria affect the biology of the cancer.”A wide-open field
No one really knows what microbes are doing in cancer, but
recent results suggest it’s not nothing. In Sällberg Chen’s study
of pancreatic cysts, for example, the researchers suspected the
bacteria might be triggering inflammation, as they’d noted
high levels of cytokines and other inflammatory markers in the
cyst fluid. Sure enough, when the researchers put the bacteria
they’d cultured from resected tumors into pancreatic cells in
vitro, including both healthy cell lines and those with oncogenic
mutations, they saw that some of the microbes caused rampant
DNA damage and eventually cell death.^3 “Some of them didn’t
do so much really, but some of them were kind of vicious,” says
Sällberg Chen. “Some of these bacteria that are hiding inside the
pancreas are probably not very good. If they are hiding there for
a long time, it will probably help [cancer] to develop.”Researchers are also looking at how the immune system responds
to bacteria in tumors. In collaboration with Wargo and others, for
example, Straussman and his Weizmann colleague Yardena Samuels
found T cells that presented peptides derived from microbes iden-
tified in the tumors.^8 “This means that in a way our immune sys-
tem really sees these bacteria,” says Straussman. Ajami, who was not
involved in the study, agrees. “We now know they’re not only there,
but they’re being detected and processed by the immune system.”
These results point to a potential mechanism by which the microbi-
ome could affect patients’ responses to therapy, Knight adds.
A handful of recent retrospective studies showing that taking
antibiotics is associated with responses to both immunotherapies
and to chemotherapies such as gemcitabine further support
the importance of the microbiome in cancer outcomes, and the
nature of the effect appears to vary by cancer type. “Antibiotics
seem to have beneficial effects in patients with pancreatic can-
cer, whereas in melanoma, antibiotics seem to have a deleteri-
ous role,” Straussman says. Indeed, researchers studying tumorThe million-dollar question now is what effect
bacteria and possibly other microbes have on tumor
development, progression, and response to treatment.
TOWARD MICROBIAL DIAGNOSTICS: Greg Sepich-Poore, cofounder of
Micronoma, prepares DNA from human plasma samples for the company’s
OncobiotaTM assay, a platform that he and his colleagues have discovered
to diagnose specific cancer types.ADAPTED FROM
SCIENCE
, 371:EABC4552, 2021; © NATASHA MUTCH, SAYOSTUDIO