{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T03:02:46Z","timestamp":1789354966660,"version":"build-2803163510"},"reference-count":250,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recent findings suggest that the gut microbiome significantly influences cancer outcomes, including responses to immune checkpoint inhibitor (ICI) treatments. Although early research focused on gut bacteria, it is now understood that the microbiome includes a bacteriome, virome, and mycobiome, all of which can modulate host immunity. Some commensal bacteria enhance anti-tumor immune responses and improve ICI efficacy, as demonstrated in both mice and patients. Fecal microbiota transplants (FMT) from patients responding to ICI have successfully reversed resistance in certain non-responders. In addition to bacteria, gut fungi and viruses are gaining attention as further factors influencing ICI effectiveness and toxicity. Recent multi-omics studies across cancer cohorts show that fungal and viral populations in the gut vary between ICI responders and non-responders. Commensal fungi may shape anti-cancer immunity by inducing inflammatory or tolerogenic pathways, while viral components can stimulate innate immune sensors that promote tumor surveillance. On the other hand, gut dysbiosis marked by expansion of pathobionts (including opportunistic fungi) and reduction in beneficial microbes is linked to serious immune-related adverse events (irAEs) such as ICI-induced colitis. This review discusses the multi-kingdom gut microbiome\u2013bacteria, fungi, and viruses\u2013and their interactions with the immune system in cancer therapy. We emphasize known mechanisms linking these microbes to anti-tumor immunity, overview human studies associating gut microbiome profiles with ICI outcomes and explore strategies to modulate the microbiome to enhance ICI efficacy while reducing toxicity. Understanding and utilizing the gut mycobiome and virome in conjunction with the bacteriome could pave the way for new biomarkers and therapeutic adjuvants in cancer immunotherapy.<\/jats:p>","DOI":"10.3390\/ijms27062538","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T12:39:08Z","timestamp":1773146348000},"page":"2538","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Across the Social Network of the Gut: Bacterial, Fungal, and Viral Determinants of Checkpoint Inhibitor Efficacy and Toxicity"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8365-0487","authenticated-orcid":false,"given":"Andreea Laura","family":"Antohi","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea Daria","family":"Gheorghi\u021b\u0103","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9053-0018","authenticated-orcid":false,"given":"Octavian","family":"Andronic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"},{"name":"Innovation and eHealth Center, Carol Davila University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6384-1822","authenticated-orcid":false,"given":"Gratiela","family":"Gradisteanu Pircalabioru","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Biology, University of Bucharest, 030018 Bucharest, Romania"},{"name":"Research Institute of University of Bucharest (ICUB), University of Bucharest, 050095 Bucharest, Romania"},{"name":"eBio-Hub Centre of Excellence in Bioengineering, National University of Science and Technology Politehnica Bucharest, 060042 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9232-8063","authenticated-orcid":false,"given":"Andreea-Ramona","family":"Treteanu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"},{"name":"Innovation and eHealth Center, Carol Davila University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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