@article{3089259,
    title = "Tumor infiltration by FcIγRIII (CD16)+ myeloid cells is associated with improved survival in patients with colorectal carcinoma",
    author = "Sconocchia, G. and Zlobec, I. and Lugli, A. and Calabrese, D. and Iezzi, G. and Karamitopoulou, E. and Patsouris, E.S. and Peros, G. and Horcic, M. and Tornillo, L. and Zuber, M. and Droeser, R. and Muraro, M.G. and Mengus, C. and Oertli, D. and Ferrone, S. and Terracciano, L. and Spagnoli, G.C.",
    journal = "International Journal  of Cancer",
    year = "2011",
    volume = "128",
    number = "11",
    pages = "2663-2672",
    issn = "0020-7136",
    doi = "10.1002/ijc.25609",
    keywords = "CD11b antigen;  CD16 antigen;  CD33 antigen;  CD45 antigen;  CD56 antigen;  CD57 antigen;  CD64 antigen;  glycoprotein p 15095;  Fc receptor, adult;  aged;  article;  bone marrow cell;  cancer survival;  CD3+ T lymphocyte;  CD8+ T lymphocyte;  cell infiltration;  colorectal carcinoma;  controlled study;  female;  human;  human tissue;  inflammatory infiltrate;  lymphocytic infiltration;  macrophage;  major clinical study;  male;  metastasis;  natural killer cell;  overall survival;  priority journal;  prognosis;  survival time;  tumor microenvironment;  cancer invasion;  cellular immunity;  colorectal tumor;  enzyme immunoassay;  flow cytometry;  immunology;  metabolism;  middle aged;  mortality;  tissue microarray;  tumor associated leukocyte, Adult;  Aged;  Aged, 80 and over;  Colorectal Neoplasms;  Female;  Flow Cytometry;  Humans;  Immunity, Cellular;  Immunoenzyme Techniques;  Killer Cells, Natural;  Lymphocytes, Tumor-Infiltrating;  Male;  Middle Aged;  Myeloid Cells;  Neoplasm Invasiveness;  Prognosis;  Receptors, IgG;  Tissue Array Analysis",
    abstract = "The prognostic significance of macrophage and natural killer (NK) cell infiltration in colorectal carcinoma (CRC) microenvironment is unclear. We investigated the CRC innate inflammatory infiltrate in over 1,600 CRC using two independent tissue microarrays and immunohistochemistry. Survival time was assessed using the Kaplan-Meier method and Cox proportional hazards regression analysis in a multivariable setting. Spearman's rank correlation tested the association between macrophage and lymphocyte infiltration. The Basel study included over 1,400 CRCs. The level of CD16+ cell infiltration correlated with that of CD3+ and CD8+ lymphocytes but not with NK cell infiltration. Patients with high CD16+ cell infiltration (score 2) survived longer than patients with low (score 1) infiltration (p = 0.008), while no survival difference between patients with score 1 or 2 for CD56+ (p = 0.264) or CD57+ cell (p = 0.583) infiltration was detected. CD16+ infiltrate was associated with improved survival even after adjusting for known prognostic factors including pT, pN, grade, vascular invasion, tumor growth and age [(p = 0.001: HR (95% CI) = 0.71 (0.6-0.9)]. These effects were independent from CD8+ lymphocyte infiltration [(p = 0.036: HR (95% CI) = 0.81 (0.7-0.9)] and presence of metastases [(p = 0.002: HR (95% CI) = 0.43 (0.3-0.7)]. Phenotypic studies identified CD16+ as CD45+CD33+CD11b+CD11c+ but CD64- HLA-DR-myeloid cells. Beneficial effects of CD16+ cell infiltration were independently validated by a study carried out at the University of Athens confirming that patients with CD16 score 2 survived longer than patients with score 1 CRCs (p = 0.011). Thus, CD16+ cell infiltration represents a novel favorable prognostic factor in CRC. © 2010 UICC."
}