title: Tumor infiltration by FcγRIII (CD16)+ myeloid cells is associated with improved survival in patients with colorectal carcinoma.
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.
authors: Department of Medicine, Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy. giuseppe.sconocchia@cnr.it
authors: Giuseppe
authors: G
authors: Sconocchia
authors: Inti
authors: I
authors: Zlobec
authors: Alessandro
authors: A
authors: Lugli
authors: Diego
authors: D
authors: Calabrese
authors: Giandomenica
authors: G
authors: Iezzi
authors: Eva
authors: E
authors: Karamitopoulou
authors: Efstratios S
authors: ES
authors: Patsouris
authors: George
authors: G
authors: Peros
authors: Milo
authors: M
authors: Horcic
authors: Luigi
authors: L
authors: Tornillo
authors: Markus
authors: M
authors: Zuber
authors: Raoul
authors: R
authors: Droeser
authors: Manuele G
authors: MG
authors: Muraro
authors: Chantal
authors: C
authors: Mengus
authors: Daniel
authors: D
authors: Oertli
authors: Soldano
authors: S
authors: Ferrone
authors: Luigi
authors: L
authors: Terracciano
authors: Giulio C
authors: GC
authors: Spagnoli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000401:mortality* / Q000556:secondary; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007124:Immunoenzyme Techniques; D007694:Killer Cells, Natural; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D017452:Receptors, IgG / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D017452:Receptors, IgG