Immune enhancement of skin carcinogenesis by CD4+ T cells

Dylan Daniel, Nicole Meyer-Morse, Emily K. Bergsland, Kerstin Dehne, Lisa M. Coussens, Douglas Hanahan

Research output: Contribution to journalArticlepeer-review

138 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1017-1028
Number of pages12
JournalJournal of Experimental Medicine
Volume197
Issue number8
DOIs
StatePublished - Apr 21 2003
Externally publishedYes

Keywords

  • Cancer
  • Inflammation
  • Lymphocyte
  • Mice
  • Transgenic

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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