{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:34:00Z","timestamp":1792528440830,"version":"4.5.0"},"reference-count":17,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:00:00Z","timestamp":1692921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Camu camu (CC) is a prebiotic that selectively stimulates growth and activity of beneficial gut microbiota. Work in murine models demonstrated that castalagin, the active compound in CC, preferentially binds to beneficial gut microbiome bacteria, promoting a stronger CD8+T cell anti-cancer response. We present two patients with metastatic melanoma whose cancer progressed on immune checkpoint inhibitors (ICIs) and developed clinically significant immune-related adverse events (irAEs). They were rechallenged with ICIs in combination with CC. The first patient is a 71-year-old woman with metastatic melanoma, whose ICI treatment was complicated by immune-related pneumonitis and colitis. Upon progression on maintenance nivolumab, CC was added to nivolumab, leading to a near complete response (CR). The second patient is a 90-year-old man with recurrent unresectable melanoma, treated with nivolumab, complicated by immune-related rash and diabetes. He developed new subcutaneous calf lesions and a metastatic popliteal lymph node. CC was added to nivolumab. One month later, the patient experienced a CR. Both patients have been on nivolumab and CC with durable responses for more than a year, with minimal irAEs. These two cases suggest that CC may modulate the microbiome, synergizing with ICIs to produce deep, durable responses with minimal irAEs.<\/jats:p>","DOI":"10.3390\/curroncol30090570","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T06:57:35Z","timestamp":1693205855000},"page":"7852-7859","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Two Cases of Durable and Deep Responses to Immune Checkpoint Inhibition-Refractory Metastatic Melanoma after Addition of Camu Camu Prebiotic"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6066-8083","authenticated-orcid":false,"given":"Steph A.","family":"Pang","sequence":"first","affiliation":[{"name":"Lady Davis Institute and Segal Cancer Centre, Jewish General Hospital, Departments of Medicine and Oncology, McGill University, Montr\u00e9al, QC H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arielle","family":"Elkrief","sequence":"additional","affiliation":[{"name":"Hematology-Oncology Division, Department of Medicine, Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Montr\u00e9al, QC H2X 3E4, Canada"},{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H2X 3E4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9600-7690","authenticated-orcid":false,"given":"Mariana Pilon","family":"Capella","sequence":"additional","affiliation":[{"name":"Lady Davis Institute and Segal Cancer Centre, Jewish General Hospital, Departments of Medicine and Oncology, McGill University, Montr\u00e9al, QC H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Wilson H.","family":"Miller","sequence":"additional","affiliation":[{"name":"Lady Davis Institute and Segal Cancer Centre, Jewish General Hospital, Departments of Medicine and Oncology, McGill University, Montr\u00e9al, QC H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1126\/science.abf3363","article-title":"Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients","volume":"371","author":"Davar","year":"2021","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/s41591-022-01694-6","article-title":"Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: A randomized phase 1 trial","volume":"28","author":"Dizman","year":"2022","journal-title":"Nat. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9533","DOI":"10.1200\/JCO.2022.40.16_suppl.9533","article-title":"Fecal microbiota transplantation followed by anti\u2013PD-1 treatment in patients with advanced melanoma","volume":"40","author":"Miller","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1038\/s41591-023-02453-x","article-title":"Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: A phase I trial","volume":"29","author":"Routy","year":"2023","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1126\/science.abb5920","article-title":"Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients","volume":"371","author":"Baruch","year":"2021","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1158\/2159-8290.CD-21-0808","article-title":"A Natural Polyphenol Exerts Antitumor Activity and Circumvents Anti-PD-1 Resistance through Effects on the Gut Microbiota","volume":"12","author":"Messaoudene","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1075593","DOI":"10.3389\/fonc.2023.1075593","article-title":"A systematic review and meta-analysis evaluating the impact of antibiotic use on the clinical outcomes of cancer patients treated with immune checkpoint inhibitors","volume":"13","author":"Crespin","year":"2023","journal-title":"Front. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ijid.2021.03.063","article-title":"Use of antibiotics is associated with worse clinical outcomes in patients with cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis","volume":"106","author":"Belani","year":"2021","journal-title":"Int. J. Infect Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1001\/jamaoncol.2019.2785","article-title":"Association of Prior Antibiotic Treatment with Survival and Response to Immune Checkpoint Inhibitor Therapy in Patients with Cancer","volume":"5","author":"Pinato","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_10","unstructured":"Health Canada Licensed Natural Health Products Database (LNHPD) (2023, July 01). Government of Canada. Available online: https:\/\/health-products.canada.ca\/lnhpd-bdpsnh\/info.do?licence=80042046."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"LBA104-LBA","DOI":"10.1200\/JCO.2023.41.17_suppl.LBA104","article-title":"Effect of CBM588 in combination with cabozantinib plus nivolumab for patients (pts) with metastatic renal cell carcinoma (mRCC): A randomized clinical trial","volume":"41","author":"Ebrahimi","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1056\/NEJMoa2026982","article-title":"Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma","volume":"384","author":"Choueiri","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.annonc.2023.02.011","article-title":"First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial)","volume":"34","author":"Spreafico","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1126\/science.aac4255","article-title":"Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy","volume":"350","author":"Sivan","year":"2015","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.eururo.2020.07.011","article-title":"Stool Microbiome Profiling of Patients with Metastatic Renal Cell Carcinoma Receiving Anti-PD-1 Immune Checkpoint Inhibitors","volume":"78","author":"Salgia","year":"2020","journal-title":"Eur. Urol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jjcc.2008.06.004","article-title":"Tropical fruit camu-camu (Myrciaria dubia) has anti-oxidative and anti-inflammatory properties","volume":"52","author":"Inoue","year":"2008","journal-title":"J. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Do, N.Q., Zheng, S., Park, B., Nguyen, Q.T.N., Choi, B.R., Fang, M., Kim, M., Jeong, J., Choi, J., and Yang, S.-J. (2021). Camu-Camu Fruit Extract Inhibits Oxidative Stress and Inflammatory Responses by Regulating NFAT and Nrf2 Signaling Pathways in High Glucose-Induced Human Keratinocytes. Molecules, 26.","DOI":"10.3390\/molecules26113174"}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/30\/9\/570\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:39:20Z","timestamp":1760128760000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/30\/9\/570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,25]]},"references-count":17,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["curroncol30090570"],"URL":"https:\/\/doi.org\/10.3390\/curroncol30090570","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,25]]}}}