Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer Journal Article


Authors: Sato, E.; Olson, S. H.; Ahn, J.; Bundy, B.; Nishikawa, H.; Qian, F.; Jungbluth, A. A.; Frosina, D.; Gnjatic, S.; Ambrosone, C.; Kepner, J.; Odunsi, T.; Ritter, G.; Lele, S.; Chen, Y. T.; Ohtani, H.; Old, L. J.; Odunsi, K.
Article Title: Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer
Abstract: In a recent report, [Zhang et al. (2003) N. Engl. J. Med. 348, 203-213], the presence of CD3+ tumor-infiltrating lymphocytes (TILs) was found to correlate with improved survival in epithelial ovarian cancer. We performed immunohistochemical analysis for TILs and cancer testis antigens in 117 cases of epithelial ovarian cancer. The interrelationship between subpopulations of TILs and expression of cancer testis antigens was investigated, as well as between TILs and overall survival. The median follow-up of the patients was 31 months. Patients with higher frequencies of intraepithelial CD8+ T cells demonstrated improved survival compared with patients with lower frequencies [median = 55 versus 26 months; hazard ratio = 0.33; confidence interval (C.I.) = 0.18-0.60; P = 0.0003]. No association was found for CD3+ TILs or other subtypes of intraepithelial or stromal TILs. However, the subgroups with high versus low intraepithelial CD8+/CD4+ TIL ratios had median survival of 74 and 25 months, respectively (hazard ratio = 0.30; C.I. = 0.16-0.55; P = 0.0001). These results indicate that CD4+ TILs influence the beneficial effects of CD8+ TIL. This unfavorable effect of CD4+ T cells on prognosis was found to be due to CD25 +forkhead box P3 (FOXP3)+ regulatory T cells (Treg; suppressor T cells), as indicated by survival of patients with high versus low CD8+/Treg ratios (median = 58 versus 23 months; hazard ratio = 0.31; C.I. = 0.17-0.58; P = 0.0002). The favorable prognostic effect of intraepithelial CD8+ TILs did not correlate with concurrent expression of NY-E5O-1 or MAGE antigens. We conclude that intraepithelial CD8+ TILs and a high CD8+/Treg ratio are associated with favorable prognosis in epithelial ovarian cancer. © 2005 by The National Academy of Sciences of the USA.
Keywords: immunohistochemistry; adult; cancer survival; human tissue; aged; aged, 80 and over; middle aged; survival rate; major clinical study; overall survival; transcription factor foxp3; antigen expression; tumor associated leukocyte; cd8-positive t-lymphocytes; lymphocytes, tumor-infiltrating; ovarian neoplasms; ovary cancer; regulatory t lymphocyte; t-lymphocytes, regulatory; cancer testis antigen; ny eso 1 antigen; melanoma antigen; cd8+ t cell; cd4-cd8 ratio
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 102
Issue: 51
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2005-01-01
Start Page: 18538
End Page: 18543
Language: English
DOI: 10.1073/pnas.0509182102
PUBMED: 16344461
PROVIDER: scopus
PMCID: PMC1311741
DOI/URL:
Notes: --- - "Cited By (since 1996): 493" - "Export Date: 24 October 2012" - "CODEN: PNASA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Eiichi Sato
    15 Sato
  2. Sara H Olson
    213 Olson
  3. Sacha Gnjatic
    111 Gnjatic
  4. Achim Jungbluth
    341 Jungbluth
  5. Gerd Ritter
    158 Ritter
  6. Lloyd J Old
    386 Old
  7. Denise Frosina
    84 Frosina