Sucralose and immunotherapy response in cancer
What it found
In people with cancer and in mice, high sucralose intake was linked to poorer response to immunotherapy.
In mice, sucralose changed gut bacteria and T-cell function, and arginine or citrulline supplements restored the response.
What they found
Studies in people
Response in people
In patients with advanced melanoma or NSCLC, high sucralose intake (more than 0.16 mg/kg/day) was linked to lower response rates and shorter progression-free survival. In high-risk resectable melanoma, high intake was linked to lower major pathologic response and shorter relapse-free survival.
Animal and lab studies
Tumor growth in mice
Mice given sucralose in drinking water had worse responses to anti-PD-1 therapy, with increased tumor growth and reduced survival in melanoma and colorectal cancer models. Sucrose (table sugar) had no such effect.
T-cell function
In mice, sucralose consumption led to T-cell exhaustion and reduced T-cell metabolism and function. In lab tests, sucralose directly slowed T-cell proliferation and reduced their ability to kill target cells.
Gut bacteria changes
Sucralose changed the gut microbiome in mice, increasing some Gram-positive bacteria. Fecal transfers from sucralose-fed mice made other mice resistant to anti-PD-1, and antibiotics or fecal transfers from responder mice restored the response.
Arginine and citrulline
Sucralose reduced arginine levels in the gut, blood, and tumor fluid of mice. Adding arginine or citrulline to the drinking water restored T-cell function and immunotherapy response.
What the authors conclude
“Overall, sucralose consumption destabilizes the gut microbiota, resulting in compromised T-cell function and ablated immune checkpoint inhibitor response in cancer.”
Also in their conclusions
- They conclude that high sucralose intake is associated with poorer immunotherapy outcomes in patients with melanoma and NSCLC.
- They suggest that sucralose consumption destabilizes the gut microbiota, leading to T-cell dysfunction and resistance to immune checkpoint inhibitors.
- They call for future prospective studies to assess whether sucralose causes immunotherapy resistance.
How it was done
The gut microbiome affects how well cancer immunotherapy works, and diet can change the microbiome. The authors wanted to know whether sucralose, a common sweetener, might affect immunotherapy outcomes.
They studied 91 patients with advanced melanoma, 41 with advanced NSCLC, and 25 with high-risk resectable melanoma who received immunotherapy. They also gave sucralose to mice with melanoma or colorectal cancer and measured tumor growth, T-cell function, and gut bacteria.
What it can’t tell you
- The human part of this study can show a link between sucralose intake and immunotherapy response, but it cannot prove that sucralose causes the poorer outcomes.
- The mouse and lab experiments cannot show exactly what happens in people.
Who paid
- Funding
- Funded by National Institutes of Health (NIH); Gateway Foundation (Gateway); Damon Runyon Cancer Research Foundation (DRCRF); NCI NIH HHS; NIAID NIH HHS; NIGMS NIH HHS; NIH HHS (from the PubMed record).
- Conflicts
- Z.L. Dahmani reports grants from NIH during the conduct of the study. L.P. Kane reports grants from NIH during the conduct of the study. G.M. Delgoffe reports grants and personal fees from Novasenta and RemplirBio outside the submitted work. D. Davar reports other support from Immunocore, Replimmune, Castle Biosciences, Regeneron, mBiomics, and Zola, personal fees from ACM Bio, Ascendis, Castle, Clinical Care Options, Gerson Lehrman Group, Immunitas, Medical Learning Group, Replimmune, Trisalus, and Xilio Therapeutics, and grants from Arcus, Immunocore, Merck, Regeneron, and Tesaro/GSK,\ outside the submitted work, as well as Intellectual Property: US Patent 63/124,231, “Compositions and Methods for Treating Cancer”, December 11, 2020 and US Patent 63/208,719, “Compositions and Methods For Responsiveness to Immune Checkpoint Inhibitors (ICI), Increasing Effectiveness of ICI and Treating Cancer”, June 9, 2021. No disclosures were reported by the other authors.
- Authors work at
- UPMC Hillman Cancer Center, Pennsylvania; University of Pittsburgh, Pennsylvania; Center for Systems Immunology, Pennsylvania
The paper
- Title
- Sucralose Consumption Ablates Cancer Immunotherapy Response through Microbiome Disruption
- Type
- Study
- Evidence
- Studies in people · animals · lab
- Summarised from
- Full text
- Cite
- Morder KM, Nguyen M, Wilfahrt DN, et al (2025). Sucralose Consumption Ablates Cancer Immunotherapy Response through Microbiome Disruption. Cancer discovery. doi:10.1158/2159-8290.CD-25-0247Free full textPubMed 40742298DOI
Summary written 26 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error