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PMID: 12695493 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Immune enhancement of skin carcinogenesis by CD4+ T cells.

The Journal of experimental medicine ·Vol. 197 ·No. 8 ·2003-04-21 ·Pages 1017-28

Daniel D, Meyer-Morse N, Bergsland EK, Dehne K, Coussens LM, Hanahan D

Abstract

In a transgenic model of multi-stage squamous carcinogenesis induced by human papillomavirus (HPV) oncogenes, infiltrating CD4+ T cells can be detected in both premalignant and malignant lesions. The lymph nodes that drain sites of epidermal neoplasia contain activated CD4+ T cells predominantly reactive toward Staphylococcal bacterial antigens. HPV16 mice deficient in CD4+ T cells were found to have delayed neoplastic progression and a lower incidence of tumors. This delay in carcinogenesis is marked by decreased infiltration of neutrophils, and reduced activity of matrix metalloproteinase-9, an important cofactor for tumor progression in this model. The data reveal an unexpected capability of CD4 T cells, whereby, proinflammatory CD4+ T cells, apparently responding to bacterial infection of dysplastic skin lesions, can inadvertently enhance neoplastic progression to invasive cancer.

MeSH Terms
Animals Antigens, Bacterial/immunology CD4-Positive T-Lymphocytes/immunology,metabolism CD8-Positive T-Lymphocytes/immunology,metabolism Carcinoma, Squamous Cell/immunology,metabolism,pathology Disease Models, Animal Humans Interferon-gamma/immunology,metabolism Lymph Nodes/immunology,metabolism Lymphocyte Activation Macrophage-1 Antigen/genetics,metabolism Matrix Metalloproteinase 9/metabolism Mice Mice, Transgenic Papillomaviridae/genetics,metabolism Skin Neoplasms/immunology,metabolism,pathology Staphylococcus aureus/immunology,metabolism Staphylococcus epidermidis/immunology,metabolism
Chemicals
Antigens, Bacterial Macrophage-1 Antigen Interferon-gamma Matrix Metalloproteinase 9
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Daniel Dylan
Department of Biochemistry and Biophysics, Diabetes and Comprehensive Cancer Centers, University of California at San Francisco, 94143, USA.
Meyer-Morse Nicole
Bergsland Emily K
Dehne Kerstin
Coussens Lisa M
Hanahan Douglas
References (42)
42 references, click to expand
  1. Human papillomavirus genotype 16 vaccines for cervical cancer prophylaxis and treatment.
    Curr Opin Oncol. 2000 Sep;12(5):466-73 PMID: 10975555
  2. The disease spectrum of Helicobacter pylori: the immunopathogenesis of gastroduodenal ulcer and gastric cancer.
    Annu Rev Microbiol. 2000;54:615-40 PMID: 11018139
  3. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis.
    Nat Cell Biol. 2000 Oct;2(10):737-44 PMID: 11025665
  4. Inflammation and cancer: back to Virchow?
    Lancet. 2001 Feb 17;357(9255):539-45 PMID: 11229684
  5. Cross-presentation, dendritic cells, tolerance and immunity.
    Annu Rev Immunol. 2001;19:47-64 PMID: 11244030
  6. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy.
    J Exp Med. 2001 Mar 19;193(6):727-40 PMID: 11257139
  7. Inflammatory cells and cancer: think different!
    J Exp Med. 2001 Mar 19;193(6):F23-6 PMID: 11257144
  8. Intestinal microflora are necessary for development of spontaneous adenocarcinoma of the large intestine in T-cell receptor beta chain and p53 double-knockout mice.
    Cancer Res. 2001 Mar 15;61(6):2395-8 PMID: 11289103
  9. Chronic immune activation and inflammation as the cause of malignancy.
    Br J Cancer. 2001 Aug 17;85(4):473-83 PMID: 11506482
  10. Regulation of cutaneous malignancy by gammadelta T cells.
    Science. 2001 Oct 19;294(5542):605-9 PMID: 11567106
  11. De novo malignancies after liver transplantation: a major cause of late death.
    Liver Transpl. 2001 Nov;7(11 Suppl 1):S109-18 PMID: 11689783
  12. The epidemiology of mesothelioma.
    Semin Oncol. 2002 Feb;29(1):18-25 PMID: 11836665
  13. Elimination of colon cancer in germ-free transforming growth factor beta 1-deficient mice.
    Cancer Res. 2002 Nov 15;62(22):6362-6 PMID: 12438215
  14. The concept of immunological surveillance.
    Prog Exp Tumor Res. 1970;13:1-27 PMID: 4921480
  15. Secretion of metalloproteinases by stimulated capillary endothelial cells. I. Production of procollagenase and prostromelysin exceeds expression of proteolytic activity.
    J Biol Chem. 1986 Feb 25;261(6):2810-3 PMID: 3005265
  16. Transgenic mouse models of self-tolerance and autoreactivity by the immune system.
    Annu Rev Cell Biol. 1990;6:493-537 PMID: 2275821
  17. CD8 is needed for development of cytotoxic T cells but not helper T cells.
    Cell. 1991 May 3;65(3):443-9 PMID: 1673361
  18. Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4.
    Nature. 1991 Sep 12;353(6340):180-4 PMID: 1832488
  19. Proteinases of the mammary gland: developmental regulation in vivo and vectorial secretion in culture.
    Development. 1991 Jun;112(2):439-49 PMID: 1794314
  20. Metalloproteinases mediate extracellular matrix degradation by cells from mouse blastocyst outgrowths.
    Development. 1992 Feb;114(2):447-56 PMID: 1317291
  21. Interactions of HPV E6 and E7 oncoproteins with tumour suppressor gene products.
    Cancer Surv. 1992;12:197-217 PMID: 1322242
  22. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori.
    Lancet. 1993 Sep 4;342(8871):575-7 PMID: 8102719
  23. Epstein-Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation.
    Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9150-4 PMID: 8415670
  24. Human T lymphocytes synthesize the 92 kDa type IV collagenase (gelatinase B).
    J Cell Physiol. 1993 Dec;157(3):644-9 PMID: 8253876
  25. Stimulatory effects of immune reactions upon the growths of untransplanted tumors.
    Cancer Res. 1994 Feb 15;54(4):908-14 PMID: 8313380
  26. Interleukin-8 expression in Helicobacter pylori infected, normal, and neoplastic gastroduodenal mucosa.
    J Clin Pathol. 1994 Jan;47(1):61-6 PMID: 8132812
  27. Progressive squamous epithelial neoplasia in K14-human papillomavirus type 16 transgenic mice.
    J Virol. 1994 Jul;68(7):4358-68 PMID: 7515971
  28. Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in human papillomavirus type 16 transgenic mice.
    Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2930-5 PMID: 8610145
  29. Genetic predisposition and parameters of malignant progression in K14-HPV16 transgenic mice.
    Am J Pathol. 1996 Dec;149(6):1899-917 PMID: 8952526
  30. Cross-species comparison of angiogenesis during the premalignant stages of squamous carcinogenesis in the human cervix and K14-HPV16 transgenic mice.
    Cancer Res. 1997 Apr 1;57(7):1294-300 PMID: 9102216
  31. Different cytokine profile and antigen-specificity repertoire in Helicobacter pylori-specific T cell clones from the antrum of chronic gastritis patients with or without peptic ulcer.
    Eur J Immunol. 1997 Jul;27(7):1751-5 PMID: 9247587
  32. Presentation of the HPV16E7 protein by skin grafts is insufficient to allow graft rejection in an E7-primed animal.
    Virology. 1997 Aug 18;235(1):94-103 PMID: 9300040
  33. Women and HIV. Epidemiology and global overview.
    Obstet Gynecol Clin North Am. 1997 Dec;24(4):705-29 PMID: 9430163
  34. Immune pathogenesis of hepatocellular carcinoma.
    J Exp Med. 1998 Jul 20;188(2):341-50 PMID: 9670046
  35. Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.
    Am J Pathol. 1999 Apr;154(4):965-73 PMID: 10233832
  36. Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis.
    Genes Dev. 1999 Jun 1;13(11):1382-97 PMID: 10364156
  37. MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis.
    Cell. 2000 Oct 27;103(3):481-90 PMID: 11081634
  38. The hallmarks of cancer.
    Cell. 2000 Jan 7;100(1):57-70 PMID: 10647931
  39. Sensitivity of the cervical transformation zone to estrogen-induced squamous carcinogenesis.
    Cancer Res. 2000 Mar 1;60(5):1267-75 PMID: 10728686
  40. Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade.
    Cancer Res. 2000 May 1;60(9):2444-8 PMID: 10811122
  41. Enhanced growth of primary tumors in cancer-prone mice after immunization against the mutant region of an inherited oncoprotein.
    J Exp Med. 2000 Jun 5;191(11):1945-56 PMID: 10839809
  42. Anal squamous intraepithelial lesions in human immunodeficiency virus-positive men and women.
    Semin Oncol. 2000 Aug;27(4):471-9 PMID: 10950374
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20021047
Published
2003-04-21
Epub
2003-00-14
Pages
1017-28
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193878
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20021047 PMC Full Text View journal details
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