Home LiteratureArticle Details
PMID: 20715106 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Tumor infiltration by FcγRIII (CD16)+ myeloid cells is associated with improved survival in patients with colorectal carcinoma.

International journal of cancer ·Vol. 128 ·No. 11 ·2011-06-01 ·Pages 2663-72

Sconocchia G, Zlobec I, Lugli A, Calabrese D, Iezzi G, Karamitopoulou E, Patsouris ES, Peros G, Horcic M, Tornillo L, Zuber M, Droeser R, Muraro MG, Mengus C, Oertli D, Ferrone S, Terracciano L, Spagnoli GC

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.

MeSH Terms
Adult Aged Aged, 80 and over Colorectal Neoplasms/immunology,mortality,secondary Female Flow Cytometry Humans Immunity, Cellular/immunology Immunoenzyme Techniques Killer Cells, Natural Lymphocytes, Tumor-Infiltrating/immunology Male Middle Aged Myeloid Cells/immunology,metabolism Neoplasm Invasiveness Prognosis Receptors, IgG/metabolism Tissue Array Analysis
Chemicals
Receptors, IgG
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Sconocchia Giuseppe
Department of Medicine, Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy. [email protected]
Zlobec Inti
Lugli Alessandro
Calabrese Diego
Iezzi Giandomenica
Karamitopoulou Eva
Patsouris Efstratios S
Peros George
Horcic Milo
Tornillo Luigi
Zuber Markus
Droeser Raoul
Muraro Manuele G
Mengus Chantal
Oertli Daniel
Ferrone Soldano
Terracciano Luigi
Spagnoli Giulio C
References (51)
51 references, click to expand
  1. Tumour-associated macrophages as a prototypic type II polarised phagocyte population: role in tumour progression.
    Eur J Cancer. 2004 Jul;40(11):1660-7 PMID: 15251154
  2. Prognostic value of tumor-infiltrating dendritic cells in colorectal cancer: role of maturation status and intratumoral localization.
    Clin Cancer Res. 2005 Apr 1;11(7):2576-82 PMID: 15814636
  3. Reporting recommendations for tumor marker prognostic studies.
    J Clin Oncol. 2005 Dec 20;23(36):9067-72 PMID: 16172462
  4. The adaptive immunologic microenvironment in colorectal cancer: a novel perspective.
    Cancer Res. 2007 Mar 1;67(5):1883-6 PMID: 17332313
  5. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes.
    Trends Immunol. 2002 Nov;23(11):549-55 PMID: 12401408
  6. Effector memory T cells, early metastasis, and survival in colorectal cancer.
    N Engl J Med. 2005 Dec 22;353(25):2654-66 PMID: 16371631
  7. Defective infiltration of natural killer cells in MICA/B-positive renal cell carcinoma involves beta(2)-integrin-mediated interaction.
    Neoplasia. 2009 Jul;11(7):662-71 PMID: 19568411
  8. The immunopathology of sequential tumor biopsies in patients treated with interleukin-2. Correlation of response with T-cell infiltration and HLA-DR expression.
    Am J Pathol. 1987 Nov;129(2):208-16 PMID: 3499823
  9. Developmental pathways that generate natural-killer-cell diversity in mice and humans.
    Nat Rev Immunol. 2007 Sep;7(9):703-14 PMID: 17717540
  10. Identification and analysis of tumour-associated antigens in hepatocellular carcinoma.
    Br J Cancer. 2005 Mar 14;92(5):929-34 PMID: 15756260
  11. Comparative efficacy of adjuvant chemotherapy in patients with Dukes' B versus Dukes' C colon cancer: results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04)
    J Clin Oncol. 1999 May;17(5):1349-55 PMID: 10334518
  12. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer.
    N Engl J Med. 2004 Jul 22;351(4):337-45 PMID: 15269313
  13. Secretion of bioactive granulocyte-macrophage colony-stimulating factor by human colorectal carcinoma cells.
    Cancer Res. 1994 Jul 15;54(14):3700-2 PMID: 8033086
  14. The humoral immune response to head and neck cancer antigens as defined by the serological analysis of tumor antigens by recombinant cDNA expression cloning.
    Cancer Immun. 2004 Jul 16;4:5 PMID: 15255672
  15. A study of the humoral immune response of breast cancer patients to a panel of human tumor antigens identified by phage display.
    Cancer Detect Prev. 2006;30(3):248-56 PMID: 16876336
  16. Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer.
    J Clin Pathol. 2007 Oct;60(10):1112-6 PMID: 17182662
  17. Characterization of human blood dendritic cell subsets.
    Blood. 2002 Dec 15;100(13):4512-20 PMID: 12393628
  18. Malignant and non-malignant lung tissue areas are differentially populated by natural killer cells and regulatory T cells in non-small cell lung cancer.
    Lung Cancer. 2008 Jan;59(1):32-40 PMID: 17825949
  19. Antibody-based therapy for solid tumors.
    Cancer J. 2008 May-Jun;14(3):178-83 PMID: 18536557
  20. Tumor markers as clinical cancer tests--are we there yet?
    Semin Oncol. 2002 Jun;29(3):211-2 PMID: 12063673
  21. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.
    N Engl J Med. 2004 Jun 3;350(23):2335-42 PMID: 15175435
  22. Polychromatic (eight-color) slide-based cytometry for the phenotyping of leukocyte, NK, and NKT subsets.
    Cytometry A. 2005 Jun;65(2):103-15 PMID: 15830380
  23. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome.
    Science. 2006 Sep 29;313(5795):1960-4 PMID: 17008531
  24. Unique monocyte subset in patients with AIDS dementia.
    Lancet. 1997 Mar 8;349(9053):692-5 PMID: 9078201
  25. G-CSF-mobilized CD34+ cells cultured in interleukin-2 and stem cell factor generate a phenotypically novel monocyte.
    J Leukoc Biol. 2004 Dec;76(6):1214-9 PMID: 15345723
  26. Tissue microarrays for high-throughput molecular profiling of tumor specimens.
    Nat Med. 1998 Jul;4(7):844-7 PMID: 9662379
  27. Heterogeneity of human blood monocytes: the CD14+ CD16+ subpopulation.
    Immunol Today. 1996 Sep;17(9):424-8 PMID: 8854561
  28. 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology.
    J Clin Oncol. 2001 Mar 15;19(6):1865-78 PMID: 11251019
  29. The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF.
    J Immunol. 2002 Apr 1;168(7):3536-42 PMID: 11907116
  30. Dendritic cells in colorectal cancer correlate with other tumor-infiltrating immune cells.
    Cancer Immunol Immunother. 2004 Nov;53(11):978-86 PMID: 15197496
  31. The novel subset of CD14+/CD16+ blood monocytes is expanded in sepsis patients.
    Blood. 1993 Nov 15;82(10):3170-6 PMID: 7693040
  32. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis.
    Cell. 2006 Jan 27;124(2):263-6 PMID: 16439202
  33. FcRgamma activation regulates inflammation-associated squamous carcinogenesis.
    Cancer Cell. 2010 Feb 17;17(2):121-34 PMID: 20138013
  34. The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma.
    Cancer. 1997 Jun 15;79(12):2320-8 PMID: 9191519
  35. High macrophage infiltration along the tumor front correlates with improved survival in colon cancer.
    Clin Cancer Res. 2007 Mar 1;13(5):1472-9 PMID: 17332291
  36. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies.
    J Pathol. 2002 Mar;196(3):254-65 PMID: 11857487
  37. The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance.
    Immunol Rev. 2008 Apr;222:155-61 PMID: 18364000
  38. High frequency of tumor-infiltrating FOXP3(+) regulatory T cells predicts improved survival in mismatch repair-proficient colorectal cancer patients.
    Int J Cancer. 2010 Jun 1;126(11):2635-43 PMID: 19856313
  39. The inflammatory micro-environment in tumor progression: the role of tumor-associated macrophages.
    Crit Rev Oncol Hematol. 2008 Apr;66(1):1-9 PMID: 17913510
  40. Phenotype and function of a CD56+ peripheral blood monocyte.
    Leukemia. 2005 Jan;19(1):69-76 PMID: 15526027
  41. Production and characterization of monoclonal antibodies against major histocompatibility complex class I chain-related gene A.
    Tissue Antigens. 2008 Nov;72(5):431-40 PMID: 18937790
  42. GM-CSF gene expression and protein production in human colorectal cancer cell lines and clinical tumor specimens.
    Int J Cancer. 1998 Jul 29;77(3):378-85 PMID: 9663599
  43. T cell responses against tumor associated antigens and prognosis in colorectal cancer patients.
    J Transl Med. 2005 Jan 19;3(1):3 PMID: 15659244
  44. Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria.
    Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4560-5 PMID: 15070757
  45. Monoclonal antibody therapy of cancer.
    Nat Biotechnol. 2005 Sep;23(9):1147-57 PMID: 16151408
  46. The antileukemia effect of HLA-matched NK and NK-T cells in chronic myelogenous leukemia involves NKG2D-target-cell interactions.
    Blood. 2005 Nov 15;106(10):3666-72 PMID: 16046526
  47. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy.
    J Clin Oncol. 2009 Apr 20;27(12):2091-6 PMID: 19188670
  48. Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers.
    J Natl Cancer Inst. 1996 Oct 16;88(20):1456-66 PMID: 8841020
  49. Alternative membrane forms of Fc gamma RIII(CD16) on human natural killer cells and neutrophils. Cell type-specific expression of two genes that differ in single nucleotide substitutions.
    J Exp Med. 1989 Aug 1;170(2):481-97 PMID: 2526846
  50. Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB.
    Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6879-84 PMID: 10359807
  51. CD16+ monocytes in patients with cancer: spontaneous elevation and pharmacologic induction by recombinant human macrophage colony-stimulating factor.
    Blood. 1995 May 15;85(10):2910-7 PMID: 7742551
Article Info
Journal
International journal of cancer
Abbr.
Int J Cancer
ISSN
1097-0215
DOI
10.1002/ijc.25609
Email
[email protected]
Published
2011-06-01
Epub
2010-00-13
Pages
2663-72
Language
English
Region
United States
NLM ID
0042124
PMCID
PMC3426287
Subset
IM
Grants
NCI NIH HHS · P01 CA109688 · United States
NCI NIH HHS · R01 CA110249 · United States
NCI NIH HHS · R01 CA138188 · United States
External Links
PubMed source DOI: 10.1002/ijc.25609 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2