46 THE SCIENTIST | the-scientist.com
PICTURE BY DEBORAH NEJMAN FROM THE STRAUSSMAN LABmicrobiomes are acutely aware that bacteria are not always bad.
“With the microbiome it’s a yin-yang,” says McAllister. “It’s not
going to be a one-size-fits-all.”
A limitation of these studies, however, is that the effects may
not necessarily have to do with resultant changes in the tumor
microbiome, as the gut microbiome will also be affected by anti-
biotic use. “The role of the tumor microbiome independently of
the gut microbiome is a very important question,” says McAllis-
ter. “Most of the time when we are modulating the tumor micro-
biome, we are modulating the gut as well.”
Indeed, when she and her colleagues took bacteria from
pancreatic cancer patients and gave them orally to antibi-
otic-treated mice, they changed the composition of the gut
microbiome first and foremost. That said, the researchers did
see notable shifts in the tumor microbiome as well, includ-
ing increases in bacteria that were enriched in the patients’
tumors. “This data suggests that the gut microbiome can mod-
ulate the tumor microbiome, in minor part by direct translo-
cation into the tumors, but more significantly, by altering the
microbial landscape,” the authors write in their paper.^7 (See
“Where Does the Tumor Microbiome Come From?” on page
44.) And the outcome was significant: animals who’d received
microbiome transplants from long-term survivors had slower-
growing tumors than did mice who’d gotten transplants from
short-term survivors, suggesting a potential protective effect
of the bacteria.
Two studies by separate groups published in the same issue
of Science last year tested the concept of fecal transplants for
modulating response to cancer therapy in humans.9,10 These
trials showed that metastatic melanoma patients treated withfecal microbiota transplants from a treatment-responding
donor had improved responses to the same checkpoint inhibi-
tor immunotherapy the donor had received. Using fecal trans-
plant to turn a nonresponder into a responder is “an amaz-
ing event,” says Knight. Although in this case the research
focused on manipulating the gut microbiome, he adds, “it
might be possible to modify what’s in the tumor by modify-
ing what’s in the gut.”
Another possibility researchers are pursuing is the use of
bacteria themselves as cancer therapeutics. Indeed, scientists
have for years been working to engineer bacteria to seek and
destroy cancer. “Now, the more we know about the bacteria
[that] are found in tumors, probably we can use this as a new
modality of treating cancer,” says Straussman.
To be able to fully harness the power of bacteria and other
microbes to treat cancer, researchers need to better under-
stand the relationship between the two. The list of outstand-
ing questions goes on and on: How stable is the tumor micro-
biome? How does it interact with the gut microbiome? How
have the bacteria in tumors evolved in the unique microenvi-
ronment? And that’s just the microbiology side; then there’s
the cancer side. What role are the microbes playing in clonal
evolution, metastasis, response to therapy, the immune land-
scape, and so on?
“And this is a short list.... Everything that has to do with
tumor biology can now be reexamined,” says Straussman, who
says he appreciates the collaborative spirit of the small but grow-
ing field. “There’s endless directions in which we can go.” gReferences- R. Straussman et al., “Tumour micro-environment elicits innate resistance to RAF
inhibitors through HGF secretion,” Nature, 487:500–504, 2012. - L.T. Geller et al., “Potential role of intratumor bacteria in mediating tumor
resistance to the chemotherapeutic drug gemcitabine,” Science, 357:1156–60, 2017. - D. Nejman et al., “The human tumor microbiome is composed of tumor type–
specific intracellular bacteria,” Science, 368:973–80, 2020. - A. Halimi et al., “Isolation of pancreatic microbiota from cystic precursors of
pancreatic cancer with intracellular growth and DNA damaging properties,”
Gut Microbes, 13:1983101, 2021. - G.D. Poore et al., “Microbiome analyses of blood and tissues suggest cancer
diagnostic approach,” Nature, 579:567–74, 2020. - E. Zozaya-Valdés et al., “Detection of cell-free microbial DNA using a
contaminant-controlled analysis framework,” Genome Biol, 22:187, 2021. - E. Riquelme et al., “Tumor microbiome diversity and composition influence
pancreatic cancer outcomes,” Cell, 178:795–806.E12, 2019. - S. Kalaora et al., “Identification of bacteria-derived HLA-bound peptides in
melanoma,” Nature, 592:138–43, 2021. - D. Davar et al., “Fecal microbiota transplant overcomes resistance to anti–PD-1
therapy in melanoma patients,” Science, 371:595–602, 2021. - E.N. Baruch et al., “Fecal microbiota transplant promotes response in
immunotherapy-refractory melanoma patients,” Science, 371:602–609, 2021.
MICROBIAL GLOW: Bacterial RNA (orange) in human ovarian tumor
(nuclei in blue)