{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:10:54Z","timestamp":1790233854038,"version":"4.1.0"},"reference-count":57,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"35","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2005,12,10]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Tumor cell killing by anticancer drugs may be supported by their immuno- and pharmacologic effects. Chemotherapy is in fact able to (A) upregulate tumor-associated antigen expression, including carcinoembryonic antigen (CEA) or other target molecules such as thymidylate synthase (TS); and (B) downregulate tumor cell resistance to the death signals induced by tumor antigen\u2013specific cytotoxic T lymphocytes. This provides the rationale for combining chemo- and immunotherapy. <\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p> We describe the results of a translational phase II trial designed to evaluate the toxicity, antitumor activity and immunologic effects of gemcitabine + FOLFOX-4 (oxaliplatin, fluorouracil, and folinic acid) polychemotherapy followed by the subcutaneous administration of granulocyte macrophage colony-stimulating factor and low-dose interleukin-2 in colorectal carcinoma patients. The study involved 29 patients (16 males and 13 females with a mean age of 69 years), 21 of whom had received a previous line of treatment, and 19 had liver involvement. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> The treatment was well tolerated and induced very high objective response (68.9%) and disease control rates (96.5%), with an average time to progression of 12.5 months. An immunologic study of peripheral blood mononuclear cells (PBMCs) taken from 20 patients showed an enhanced proliferative response to colon carcinoma antigen and a significant reduction in suppressive regulatory T lymphocytes (CD4<jats:sup>+<\/jats:sup>CD25<jats:sub>T-reg<\/jats:sub><jats:sup>+<\/jats:sup>). A cytofluorimetric study of the PBMCs of five HLA-A(<jats:sup>\u2605<\/jats:sup>)02.01<jats:sup>+<\/jats:sup> patients who achieved an objective response showed an increased frequency of cytolytic T lymphocyte precursors specific for known CEA- and TS-derived epitopes. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> The results show that our regimen has strong immunologic and antitumor activity in colorectal cancer patients and deserves to be investigated in phase III trials. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2005.12.147","type":"journal-article","created":{"date-parts":[[2005,8,2]],"date-time":"2005-08-02T00:26:23Z","timestamp":1122942383000},"page":"8950-8958","source":"Crossref","is-referenced-by-count":141,"title":["Chemo-Immunotherapy of Metastatic Colorectal Carcinoma With Gemcitabine Plus FOLFOX 4 Followed by Subcutaneous Granulocyte Macrophage Colony-Stimulating Factor and Interleukin-2 Induces Strong Immunologic and Antitumor Activity in Metastatic Colon Cancer Patients"],"prefix":"10.1200","volume":"23","author":[{"given":"Pierpaolo","family":"Correale","sequence":"first","affiliation":[{"name":"From the Section of Medical Oncology; Section of Pathology, Department of Human Pathology and Oncology; Section of Virology, Department of Molecular Biology; Giorgio Segre Department of Pharmacology; Department of Imaging and Radiology; Interdepartmental Oncopharmacological Centre, Siena University School of Medicine, Siena; Medical Oncology and Pharmacology Section, Department of Neuroscience, Tor Vergata University, Rome, Italy; and the Experimental Oncology Section, Laboratory of Tumor Immunology and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Cusi","sequence":"additional","affiliation":[{"name":"From the Section of Medical Oncology; Section of Pathology, Department of Human Pathology and Oncology; Section of Virology, Department of Molecular Biology; Giorgio Segre Department of Pharmacology; Department of Imaging and Radiology; Interdepartmental Oncopharmacological Centre, Siena University School of Medicine, Siena; Medical Oncology and Pharmacology Section, Department of Neuroscience, Tor Vergata University, Rome, Italy; and the Experimental Oncology Section, Laboratory of Tumor Immunology and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwong Yok","family":"Tsang","sequence":"additional","affiliation":[{"name":"From the Section of Medical Oncology; Section of Pathology, Department of Human Pathology and Oncology; Section of Virology, Department of Molecular Biology; Giorgio Segre Department of Pharmacology; Department of Imaging and Radiology; Interdepartmental Oncopharmacological Centre, Siena University School of Medicine, Siena; Medical Oncology and Pharmacology Section, Department of Neuroscience, Tor Vergata University, Rome, Italy; and the Experimental Oncology Section, Laboratory of Tumor Immunology and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Del Vecchio","sequence":"additional","affiliation":[{"name":"From the Section of Medical Oncology; Section of Pathology, Department of Human Pathology and Oncology; Section of Virology, Department of Molecular Biology; Giorgio Segre Department of Pharmacology; Department of Imaging and Radiology; Interdepartmental Oncopharmacological Centre, Siena University School of Medicine, Siena; Medical Oncology and Pharmacology Section, Department of Neuroscience, Tor Vergata University, Rome, Italy; and the Experimental Oncology Section, Laboratory of Tumor Immunology and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Marsili","sequence":"additional","affiliation":[{"name":"From the Section of Medical Oncology; Section of Pathology, Department of Human Pathology and Oncology; Section of Virology, Department of Molecular Biology; Giorgio Segre Department of Pharmacology; Department of Imaging and Radiology; Interdepartmental Oncopharmacological Centre, Siena University School of Medicine, Siena; Medical Oncology and Pharmacology Section, Department of Neuroscience, Tor Vergata University, Rome, Italy; and the Experimental Oncology Section, Laboratory of Tumor Immunology and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco La","family":"Placa","sequence":"additional","affiliation":[{"name":"From the Section of Medical Oncology; Section of Pathology, Department of Human Pathology and Oncology; Section of Virology, Department of Molecular Biology; Giorgio Segre Department of Pharmacology; Department of Imaging and Radiology; Interdepartmental Oncopharmacological Centre, Siena University School of Medicine, Siena; Medical Oncology and Pharmacology Section, Department of Neuroscience, Tor Vergata University, Rome, Italy; and the Experimental Oncology Section, Laboratory of Tumor Immunology and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Intrivici","sequence":"additional","affiliation":[{"name":"From the Section of Medical Oncology; Section of Pathology, Department of Human Pathology and Oncology; Section of Virology, Department of Molecular Biology; Giorgio Segre Department of Pharmacology; Department of Imaging and Radiology; Interdepartmental Oncopharmacological Centre, Siena University School of Medicine, Siena; Medical Oncology and Pharmacology Section, Department of Neuroscience, Tor Vergata University, Rome, Italy; and the Experimental Oncology Section, Laboratory of Tumor Immunology and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Aquino","sequence":"additional","affiliation":[{"name":"From the Section of Medical Oncology; Section of Pathology, Department of Human Pathology and Oncology; Section of Virology, Department of Molecular Biology; Giorgio Segre Department of Pharmacology; Department of Imaging and Radiology; Interdepartmental Oncopharmacological Centre, Siena University School of Medicine, Siena; Medical Oncology and Pharmacology Section, Department of Neuroscience, Tor Vergata University, Rome, Italy; and the Experimental Oncology Section, Laboratory of Tumor Immunology and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Micheli","sequence":"additional","affiliation":[{"name":"From the Section of Medical Oncology; Section of Pathology, Department of Human Pathology and Oncology; Section of Virology, Department of Molecular Biology; Giorgio Segre Department of Pharmacology; Department of Imaging and Radiology; Interdepartmental Oncopharmacological Centre, Siena University School of Medicine, Siena; Medical Oncology and Pharmacology Section, Department of Neuroscience, Tor Vergata University, Rome, Italy; and the Experimental Oncology Section, Laboratory of Tumor Immunology and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Nencini","sequence":"additional","affiliation":[{"name":"From the Section of Medical Oncology; Section of Pathology, Department of Human Pathology and Oncology; Section of Virology, Department of Molecular Biology; Giorgio Segre Department of Pharmacology; Department of Imaging and Radiology; Interdepartmental Oncopharmacological Centre, Siena University School of Medicine, Siena; Medical Oncology and Pharmacology Section, Department of Neuroscience, Tor Vergata University, Rome, Italy; and the Experimental Oncology Section, Laboratory of Tumor Immunology and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Ferrari","sequence":"additional","affiliation":[{"name":"From the Section of Medical Oncology; Section of Pathology, Department of Human Pathology and Oncology; Section of Virology, Department of Molecular Biology; Giorgio Segre Department of Pharmacology; Department of Imaging and Radiology; Interdepartmental Oncopharmacological Centre, Siena University School of Medicine, Siena; Medical Oncology and Pharmacology Section, Department of Neuroscience, Tor Vergata University, Rome, Italy; and the Experimental Oncology Section, Laboratory of Tumor Immunology and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Giorgi","sequence":"additional","affiliation":[{"name":"From the Section of Medical Oncology; Section of Pathology, Department of Human Pathology and Oncology; Section of Virology, Department of Molecular Biology; Giorgio Segre Department of Pharmacology; Department of Imaging and Radiology; Interdepartmental Oncopharmacological Centre, Siena University School of Medicine, Siena; Medical Oncology and Pharmacology Section, Department of Neuroscience, Tor Vergata University, Rome, Italy; and the Experimental Oncology Section, Laboratory of Tumor Immunology and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enzo","family":"Bonmassar","sequence":"additional","affiliation":[{"name":"From the Section of Medical Oncology; Section of Pathology, Department of Human Pathology and Oncology; Section of Virology, Department of Molecular Biology; Giorgio Segre Department of Pharmacology; Department of Imaging and Radiology; Interdepartmental Oncopharmacological Centre, Siena University School of Medicine, Siena; Medical Oncology and Pharmacology Section, Department of Neuroscience, Tor Vergata University, Rome, Italy; and the Experimental Oncology Section, Laboratory of Tumor Immunology and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Francini","sequence":"additional","affiliation":[{"name":"From the Section of Medical Oncology; Section of Pathology, Department of Human Pathology and Oncology; Section of Virology, Department of Molecular Biology; Giorgio Segre Department of Pharmacology; Department of Imaging and Radiology; Interdepartmental Oncopharmacological Centre, Siena University School of Medicine, Siena; Medical Oncology and Pharmacology Section, Department of Neuroscience, Tor Vergata University, Rome, Italy; and the Experimental Oncology Section, Laboratory of Tumor Immunology and..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"BIB1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2003.01735.x"},{"key":"BIB2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.09.046"},{"key":"BIB3","doi-asserted-by":"crossref","unstructured":"Medinger M, Steinbild S, Mross K: Adjuvant and palliative anticancer treatment of colon carcinoma. Schweiz Rundsch Med Prax 93:1633,2004-1644,","DOI":"10.1024\/0369-8394.93.40.1633"},{"key":"BIB4","unstructured":"Kohne CH: Palliative therapy of colorectal cancer. Onkologie 7:41,2003-47,  (suppl)"},{"key":"BIB5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032691"},{"key":"BIB6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.05.113"},{"key":"BIB7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1999.tb01331.x"},{"key":"BIB8","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/87.13.982"},{"key":"BIB9","doi-asserted-by":"crossref","unstructured":"Dalerba P, Maccalli C, Casati C, et al: Immunology and immunotherapy of colorectal cancer. Crit Rev Oncol Hematol 46:33,2003-57,","DOI":"10.1016\/S1040-8428(02)00159-2"},{"key":"BIB10","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.23.3964"},{"key":"BIB11","unstructured":"Morse MA, Deng Y, Coleman D, et al: A phase I study of active immunotherapy with carcinoembryonic antigen peptide(CAP-1)-pulsed autologous human cultured dendritic cells in patients with metastatic malignacies expressing carcinoembryonic antigen. Clin Cancer Res 5:1331,1999-1338,"},{"key":"BIB12","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/84.14.1084"},{"key":"BIB13","unstructured":"Kantor J, Irvine K, Abrams S, et al: Immunogenicity and safety of a recombinant vaccinia virus vaccine expressing the carcinoembryonic antigen gene in a nonhuman primate. Cancer Res 52:6917,1992-6925,"},{"key":"BIB14","unstructured":"Foon K, John WJ, Chakraborty M, et al: Clinical and immune responses in advanced colorectal cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen. Clin Cancer Res 3:1267,1997-1276,"},{"key":"BIB15","unstructured":"Kass E, Schlom J, Thompson J, et al: Induction of protective host immunity to carcinoembryonic antigen (CEA), a self antigen in CEA transgenic mice, by immunizing with a recombinant vaccinia-CEA virus. Cancer Res 59:676,1999-683,"},{"key":"BIB16","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/92.6.299"},{"key":"BIB17","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1305"},{"key":"BIB18","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1997.1169"},{"key":"BIB19","doi-asserted-by":"publisher","DOI":"10.1007\/s002620100229"},{"key":"BIB20","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10969"},{"key":"BIB21","doi-asserted-by":"publisher","DOI":"10.1179\/joc.2001.13.5.519"},{"key":"BIB22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.6.3717"},{"key":"BIB23","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.2.820"},{"key":"BIB24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114525"},{"key":"BIB25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1981.tb00435.x"},{"key":"BIB26","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601783"},{"key":"BIB27","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(01)00063-6"},{"key":"BIB28","unstructured":"Boyum A: A one-stage procedure for isolation of granulocytes and lymphocytes from human blood: General sedimentation properties of white blood cells in a 1g gravity field. Scand J Clin Lab Invest 97:51,1968-76,"},{"key":"BIB29","unstructured":"Guadagni F, Witt PL, Robbins PF, et al: Regulation of carcinoembryonic antigen expression in different human colorectal tumor cells by interferon- Cancer Res 50:6248,1990-6255, \u03b1"},{"key":"BIB31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.40.25809"},{"key":"BIB32","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.9.4840"},{"key":"BIB34","unstructured":"Dubois B, Chapat L, Kaiserlian D: CD4+CD25+ T cells as key regulators of immune responses. Eur J Dermatol 13:111,2003-116,"},{"key":"BIB35","doi-asserted-by":"publisher","DOI":"10.1097\/00002371-200205000-00002"},{"key":"BIB36","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0213605"},{"key":"BIB37","doi-asserted-by":"publisher","DOI":"10.1177\/03008916000865s108"},{"key":"BIB38","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(97)80050-7"},{"key":"BIB39","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(200002)9999:9999<::AID-IJC1132>3.0.CO;2-V"},{"key":"BIB40","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204095"},{"key":"BIB41","doi-asserted-by":"publisher","DOI":"10.1089\/10430340050032375"},{"key":"BIB42","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(08)60142-8"},{"key":"BIB43","unstructured":"Aarts WM, Schlom J, Hodge JW: Vector based vaccine\/cytokine combination therapy to enhance induction of immune response to a self-antigen and anti-tumor activity. Cancer Res 62:5770,2002-5777,"},{"key":"BIB44","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80570-1"},{"key":"BIB45","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00111-X"},{"key":"BIB46","doi-asserted-by":"crossref","unstructured":"Baars A, Buter J, Pinedo HM: Making use of the primary tumor. Bioessays 25:79,2002-86,","DOI":"10.1002\/bies.10194"},{"key":"BIB47","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)07186-4"},{"key":"BIB48","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013160508133"},{"key":"BIB49","doi-asserted-by":"crossref","unstructured":"Mavligit G, Gutterman JU, Burgess MA, et al: Adjuvant immunotherapy and chemo-immunotherapy in colorectal cancer of the Dukes' C classification: Preliminary clinical results. Cancer 36:2421,1975-2427,","DOI":"10.1002\/1097-0142(197512)36:6<2421::AID-CNCR2820360623>3.0.CO;2-2"},{"key":"BIB50","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197811)42:5<2169::AID-CNCR2820420513>3.0.CO;2-V"},{"key":"BIB51","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197901)43:1<91::AID-CNCR2820430114>3.0.CO;2-R"},{"key":"BIB52","doi-asserted-by":"publisher","DOI":"10.1007\/s003450000191"},{"key":"BIB53","doi-asserted-by":"publisher","DOI":"10.1097\/00000421-199904000-00010"},{"key":"BIB54","doi-asserted-by":"publisher","DOI":"10.1177\/030089169908500617"},{"key":"BIB55","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-200102000-00013"},{"key":"BIB56","unstructured":"Bonmassar E, Bonmassar A, Vadlamudi S, et al: Antigenic change of L1210 leukemia in mice treated with 5-(3,3-dimethyl-1triazeno)-imidazole-4-carboxamide. Cancer Res 32:1446,1972-1450,"},{"key":"BIB57","unstructured":"Nowak AK, Robinson BW, Lake RA: Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors. Cancer Res 63:4490,2003-4496,"},{"key":"BIB58","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.10.4905"},{"key":"BIB59","unstructured":"Nowak AK, Robinson BW, Lake RA: Gemcitabine exerts a selective effect on the humoral immune-response: implications for combination chemo-immunotherapy. Cancer Res 62:2353,2002-2358,"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2005.12.147","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T20:38:49Z","timestamp":1653511129000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2005.12.147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,12,10]]},"references-count":57,"journal-issue":{"issue":"35","published-print":{"date-parts":[[2005,12,10]]}},"alternative-id":["10.1200\/JCO.2005.12.147"],"URL":"https:\/\/doi.org\/10.1200\/jco.2005.12.147","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,12,10]]}}}