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Predictive immune biomarkers: an unattainable chimera?

Cellular & Molecular Immunology 2018年第8期15卷 740-742页

作者： Anna Maria Trotta Roberto Pacelli stefania scala Functional Genomics Istituto Nazionale per lo Studio e la Cura dei TumoriFondazione‘G.Pascale’Via SemmolaNaplesItaly Dipartimento di Scienze Biomediche Avanzate.UniversitàFederico II.Via Pansini NaplesItaly

Immune checkpoint blockade(ICB)with antibodies interfering with cytotoxic T lymphocyte antigen 4(CTLA-4)and the programmed cell death 1(PD-1)protein tremendously revolutionized therapy for advanced ***,the activity of such agents(ipilimumab and nivolumab)is limited to a 10–45%response rate in the context of unselected populations with advanced solid *** common cancer types have demonstrated a very low frequency of response(breast,prostate and colon cancers),and heterogeneous responses have been observed between distinct tumors within the same *** to broad clinical applicability include identifying patients most likely to benefit from checkpoint inhibitors and overcoming resistance to *** immune response is a dynamic and constantly evolving process due primarily to patient-dependent factors,including genetic and tumor microenvironment(TME)features,and secondarily to treatment interventions.

关键词： immune colon likely

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Natural killer cells activity in a metastatic colorectal cancer patient with complete and long lasting response to therapy

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World Journal of Clinical Cases 2017年第11期5卷 390-396页

作者： Alessandro Ottaiano Maria Napolitano Monica Capozzi Salvatore Tafuto Antonio Avallone stefania scala Department of Abdominal Oncology Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S. Immunology Unit Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S.

Here we report a case of a 70-year-old man who received adjuvant chemotherapy with fluorouracile, folinic acid and oxaliplatin after a left hemicolectomy for a stage Ⅲb adenocarcinoma in May 2009. During followup he de-veloped abdominal lymphnodes metastases evidenced by positron emission tomography-computed tomography(PET-CT) scan and increase of carcinoembryonic antigen(CEA) level. Chemotherapy with capecitabine, oxaliplatin and bevacizumab was started in April 2012. Restaging showed a complete response and normalization of CEA. The patient received maintenance therapy with bevacizumab which was stopped in December 2013 for patient choice. In October 2014, a new increase in CEA was documented and PET-CT scan showed lung metastases. Analysis of RAS status revealed the absence of mutations, then the patient started a second-line chemotherapy with fluorouracile, folinic acid, irinotecan(folfiri) and panitumumab achieving, in January 2015, a complete response and normalization of CEA. Thereafter, folfiri was discontinued for toxicity; furthermore, upon the third occurrence of a grade 3 dermatologic toxicity, panitumumab was continued from June 2015 at 60% of the original dose and it was administered every three weeks. Until presentation of this case, the patient maintains a complete response, has no symptoms of disease and CEA is normal. Interestingly, this patient presented a high proportion of circulating natural killer(NK) cells(35.1%) with high cytotoxic activity against tumor cells. Study on the role of NK in patients with advanced colorectal cancer are ongoing.

关键词： Colorectal cancer Panitumumab Natural killers Regulatory cells Chemotherapy

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CXCR4 expression affects overall survival of HCC patients whereas CXCR7 expression does not

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Cellular & Molecular Immunology 2015年第4期12卷 474-482页

作者： Maria Neve Polimeno Caterina Ierano Crescenzo D'Alterio Nunzia Simona Losito Maria Napolitano Luigi Portella Giosuè Scognamiglio Fabiana Tatangelo Anna Maria Trotta Steven Curley Susan Costantini Raffaele Liuzzi Francesco Izzo stefania scala Oncological Immunology Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"-IRCCS-ITALIA Naples Italy. Pathology Unit Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"-IRCCS-ITALIA Naples Italy. Department of Surgical Oncology University of Texas MD Anderson Cancer Center Houston TX USA. CROM-Centro Ricerche Oncologiche Mercogliano Mercogliano (AV) Italy. Institute of Biostructure and Bioimaging (IBB) of the Italian National Research Council Naples Italy. Hepato-Biliary Surgery Unit Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"-IRCCS-ITALIA Naples Italy.

Hepatocellular carcinoma （HCC） is a heterogeneous disease with a poor prognosis and limited markers for predicting patient survival. Because chemokines and chemokine receptors play numerous and integral roles in HCC disease progression, the CXCR4-CXCL12-CXCR7 axis was studied in HCC patients. CXCR4 and CXCR7 expression was analyzed by immunohistochemistry in 86 HCC patients （training cohort） and validated in 42 unrelated HCC patients （validation cohort）. CXCR4 levels were low in 22.1% of patients, intermediate in 30.2%, and high in 47.7%, whereas CXCR7 levels were low in 9.3% of patients, intermediate in 44.2% and high in 46.5% of the patients in the training cohort. When correlated to patient outcome, only CXCR4 affected overall survival （P=-O.03）. CXCR4-CXCL12-CXCR7 mRNA levels were examined in 33/86 patients. Interestingly, the common CXCR4-CXCR7 ligand CXCL12 was expressed at significantly lower levels in tumor tissues compared to adjacent normal liver （P=0.032）. The expression and function of CXCR4 and CXCR7 was also analyzed in several human HCC cell lines. CXCR4 was expressed in Huh7, Hep3B, SNU398, SNU449 and SNU475 cells, whereas CXCR7 was expressed in HepG2, Huh7, SNU449 and SNU475 cells. Huh7, SNU449 and SNU475 cells migrated toward CXCL12, and this migration was inhibited by AMD3 lO0/anti-CXCR4 and by CCX771/anti-CXCR7. Moreover, SNU449 and Huh7 cells exhibited matrix invasion in the presence of CXCL12 and CXCL11, a ligand exclusive to CXCR7. In conclusion, CXCR4 affects the prognosis of HCC patients but CXCR7 does not. Therefore, the CXCR4-CXCL12-CXCR7 axis plays a role in the interaction of HCC with the surrounding normal tissue and represents a suitable therapeutic target.

关键词： CXCR4 CXCR7 CXCL12 hepatocellular carcinoma prognosis

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