{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T07:00:58Z","timestamp":1774422058932,"version":"3.50.1"},"reference-count":82,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T00:00:00Z","timestamp":1574899200000},"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>This article summarizes the histories of six patients with different solid tumors treated with a new strategy based on tumor burden reduction and immune evasion as potential targets. All six patients were at a high risk of relapse and were likely to have a minimal residual disease following conventional therapy: biochemical recurrence (BCR) following radical prostatectomy (RP) (two prostate cancers patients), removal of distant metastases (one colorectal and one breast cancer), and complete response (CR) of distant metastases to conventional therapy (one breast cancer and one esophageal\u2013gastric junction cancer). Four of the patients, two after RP and BCR, one after removal of a single pulmonary metastasis from breast cancer, and one after CR to chemotherapy of peritoneal metastases and ascites from an esophageal\u2013gastric junction primary cancer, regularly received cycles of a new drug schedule with the aim of inhibiting immune suppression (IT). In these four patients, preliminary laboratory tests of peripheral blood suggested an interleukin (IL)-2\/IL-12 mediated stimulation of cellular immune response with a concomitant decrease in vascular endothelial growth factor (VEGF) immune suppression. The fifth case was a breast cancer patient with distant metastases in CR, while receiving beta-interferon and interleukin-2 in addition to conventional hormone therapy. To date, all five patients are alive and doing well and they have been unexpectedly disease-free for 201 and 78 months following BCR, 28 months following the removal of a single pulmonary metastases, 32 months following CR to chemotherapy of peritoneal metastases and ascites, and 140 months following diagnosis of multiple bone metastases, respectively. The sixth patient, who had colorectal cancer and multiple synchronous liver metastases and underwent nine surgical interventions for metastatic disease, although not disease-free, is doing well 98 months after primary surgery. Our six cases reports can be interpreted with the hypothesis that immune manipulation and\/or a concomitant low tumor burden favored their clinical outcome.<\/jats:p>","DOI":"10.3390\/ijms20235986","type":"journal-article","created":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T08:14:04Z","timestamp":1574928844000},"page":"5986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Treatment of Metastatic or High-Risk Solid Cancer Patients by Targeting the Immune System and\/or Tumor Burden: Six Cases Reports"],"prefix":"10.3390","volume":"20","author":[{"given":"Andrea","family":"Nicolini","sequence":"first","affiliation":[{"name":"Department of Oncology, Transplantation and New technologies in Medicine, University of Pisa, 56100 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Department of Oncology, Transplantation and New technologies in Medicine, University of Pisa, 56100 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7783-0262","authenticated-orcid":false,"given":"Riccardo","family":"Morganti","sequence":"additional","affiliation":[{"name":"Section of Statistics, University Hospital of Pisa, 56100 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Carpi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56100 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"R577","DOI":"10.1530\/ERC-18-0142","article-title":"Tumour growth and immune evasion as targets for a new strategy in advanced cancer","volume":"25","author":"Nicolini","year":"2018","journal-title":"Endocr. 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