Intratumoral T Cells, Recurrence, and Survival in Epithelial Ovarian Cancer
Lin Zhang, M.D., Jose R. Conejo-Garcia, M.D., Ph.D., Dionyssios Katsaros, M.D., Ph.D., Phyllis A. Gimotty, Ph.D., Marco Massobrio, M.D., Giorgia Regnani, M.D., Antonis Makrigiannakis, M.D., Ph.D., Heidi Gray, M.D., Katia Schlienger, M.D., Ph.D., Michael N. Liebman, Ph.D., Stephen C. Rubin, M.D., and George Coukos, M.D., Ph.D.
Background Although tumor-infiltrating T cells have been documentedin ovarian carcinoma, a clear association with clinical outcomehas not been established.
Methods We performed immunohistochemical analysis of 186 frozenspecimens from advanced-stage ovarian carcinomas to assess thedistribution of tumor-infiltrating T cells and conducted outcomeanalyses. Molecular analyses were performed in some tumors byreal-time polymerase chain reaction.
Results CD3+ tumor-infiltrating T cells were detected withintumor-cell islets (intratumoral T cells) in 102 of the 186 tumors(54.8 percent); they were undetectable in 72 tumors (38.7 percent);the remaining 12 tumors (6.5 percent) could not be evaluated.There were significant differences in the distributions of progression-freesurvival and overall survival according to the presence or absenceof intratumoral T cells (P<0.001 for both comparisons). Thefive-year overall survival rate was 38.0 percent among patientswhose tumors contained T cells and 4.5 percent among patientswhose tumors contained no T cells in islets. Significant differencesin the distributions of progression-free survival and overallsurvival according to the presence or absence of intratumoralT cells (P<0.001 for both comparisons) were also seen among74 patients with a complete clinical response after debulkingand platinum-based chemotherapy: the five-year overall survivalrate was 73.9 percent among patients whose tumors containedT cells and 11.9 percent among patients whose tumors containedno T cells in islets. The presence of intratumoral T cells independentlycorrelated with delayed recurrence or delayed death in multivariateanalysis and was associated with increased expression of interferon-,interleukin-2, and lymphocyte-attracting chemokines within thetumor. The absence of intratumoral T cells was associated withincreased levels of vascular endothelial growth factor.
Conclusions The presence of intratumoral T cells correlateswith improved clinical outcome in advanced ovarian carcinoma.
Source Information
From the Abramson Family Cancer Research Institute (L.Z., K.S., M.N.L., G.C.), the Center for Research on Reproduction and Women's Health (L.Z., J.R.C.-G., G.R., H.G., G.C.), the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology (S.C.R., G.C.), and the Department of Biostatistics and Epidemiology (P.A.G.), University of Pennsylvania, Philadelphia; the Department of Obstetrics and Gynecology, University of Turin, Turin, Italy (D.K., M.M.); and the Department of Obstetrics and Gynecology, University of Heraklion, Heraklion, Greece (A.M.). Drs. Zhang, Conejo-Garcia, and Katsaros contributed equally to the article.
Address reprint requests to Dr. Coukos at the Center for Research on Reproduction and Women's Health, University of Pennsylvania, 1355 Biomedical Research Bldg. II/III, 421 Curie Blvd., Philadelphia, PA 19104, or at gcks{at}mail.med.upenn.edu.
T Cells in Ovarian Cancer
Fraggetta F., Scollo P., Pelosi G., Coukos G., Zhang L., Conejo-Garcia J. R.
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N Engl J Med 2003;
348:1814, May 1, 2003.
Correspondence
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, interleukin-2, and lymphocyte-attracting chemokines within the tumor. The absence of intratumoral T cells was associated with increased levels of vascular endothelial growth factor. 
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