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Keywords:

  • CD25+;
  • CD4+;
  • FOXP3+;
  • induced regulatory T cells;
  • natural regulatory T cells;
  • TGFβ

Problem  Thriving of tumors amidst rich immune infiltrates is an unexplained paradox.

Method of study  Immune markers on lymphocytic infiltrates in HPV-positive cervicitis, cervical intraepithelial neoplasia III (CIN III), squamous cell carcinoma (SCC) and normal cervices were characterized immunohistochemically. Regulatory T cells were enumerated and phenotypically characterized using antibodies to FOXP3.

Results  SCCs had higher numbers of CD4 and CD8 cells; infiltrates expressed more CD25, TGFβ, and IL10 but had significantly lower IL2 compared with cervicitis and CIN III. Expression of CD25 and IL2 correlated well in cervicitis and CIN III but not in SCC. FOXP3 expression was also higher and ratios of CD4/FOXP3 and CD8/FOXP3 were lower in SCC. A fraction of cervicitis, CIN I, CIN II and CIN III had natural (n) regulatory T cells (Tregs); their lesional distribution was predominantly intraepithelial in cervicitis, while in CIN they were also present in the stroma. The proportion of FOXP3+ CD25+; FOXP3+ CD25 and TGFβ+ CD25+ in invasive tumors was 17; 19 and 22 respectively.

Conclusion  Cervical tumors are marked by the presence of an immunoregulatory environment, and harbor equal proportions of ‘inactive’ n Tregs; activated n Tregs; and Tregs operating via TGFβ. nTregs in cervicitis and CIN may be a potential marker of persistence.