Tumor-host interaction: Analysis of cytokines, growth factors, and tumor-infiltrating lymphocytes in ovarian carcinomas

被引:104
作者
Merogi, AJ
Marrogi, AJ
Ramesh, R
Robinson, WR
Fermin, CD
Freeman, SM
机构
[1] TULANE UNIV,SCH MED,DEPT PATHOL & LAB MED,MED CTR,NEW ORLEANS,LA 70112
[2] TULANE UNIV,MED CTR,DEPT OBSTET & GYNECOL,NEW ORLEANS,LA 70112
关键词
ovarian cancer; PCR; immunohistochemistry; tumorinfiltrating; lymphocytes;
D O I
10.1016/S0046-8177(97)90131-3
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
The host-tumor interaction may play an important role in determining tumor progress. Recent studies have shown that this interaction can be influenced by the release of soluble factors by tumor cells and tumor-infiltrating lymphocytes (TIL). The aim of our study is to characterize the nature of cytokines and growth factors and their relationship to the cellular infiltrates in 16 patients with ovarian cancer using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. Total RNA from 20 malignant and 10 benign specimens were used to assay for expression of 12 cytokines. Additionally, monoclonal antibodies (MAbs) were used to detect T cells, CD4(+) helper and CD8(+) cytotoxic/suppressor T-cell subtypes, B cells, and macrophages. Our results showed the expression of transforming growth factor-beta(1) (TGF-beta(1)), interleukin-10 (IL-10), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in 19, 17, and 10 malignant specimens, P < .001, .001, and .05, respectively. Other cytokines such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), TNF-beta/LT, IL-2, and IL-6 were expressed in a few cases, and IL-1 alpha and IL-4 expression were not detected. The benign samples did not express IL-10, but GM-CSF, TGF-beta(1), and IL-8 were expressed in one, one, and four specimens, respectively. Interestingly, in four cases in which samples from the primary and relapse tumors were available for analysis, the tumors in relapse showed a significant increase for TGF-beta(1) (P < .05) and a decreased trend in IL-10 mRNA levels. The source of these factors was tumor cells as detected immunohistochemically. This combined alteration of TGF-beta(1) and IL-10 was associated with a significant reduction in number of TIL in general, and CD8(+) and macrophages in particular (P = .036 and .049, respectively). Our findings suggest the important role of certain soluble factors in the complex process of tumor progression. Furthermore, understanding the tumor-host relationship and the factors influencing the interaction may be helpful in developing effective and innovative treatment methods. Copyright (C) 1997 by W.B. Saunders Company.
引用
收藏
页码:321 / 331
页数:11
相关论文
共 56 条
[41]  
RUEGEMER JJ, 1990, J IMMUNOL, V144, P1767
[42]   THE GLIOBLASTOMA-DERIVED T-CELL SUPPRESSOR FACTOR TRANSFORMING GROWTH FACTOR-BETA-2 INHIBITS T-CELL GROWTH WITHOUT AFFECTING THE INTERACTION OF INTERLEUKIN-2 WITH ITS RECEPTOR [J].
SIEPL, C ;
BODMER, S ;
FREI, K ;
MACDONALD, HR ;
DEMARTIN, R ;
HOFER, E ;
FONTANA, A .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1988, 18 (04) :593-600
[43]   STUDIES OF THE HER-2/NEU PROTO-ONCOGENE IN HUMAN-BREAST AND OVARIAN-CANCER [J].
SLAMON, DJ ;
GODOLPHIN, W ;
JONES, LA ;
HOLT, JA ;
WONG, SG ;
KEITH, DE ;
LEVIN, WJ ;
STUART, SG ;
UDOVE, J ;
ULLRICH, A ;
PRESS, MF .
SCIENCE, 1989, 244 (4905) :707-712
[44]  
SMYTH MJ, 1991, J IMMUNOL, V146, P3289
[45]   DETECTION OF SPECIFIC SEQUENCES AMONG DNA FRAGMENTS SEPARATED BY GEL-ELECTROPHORESIS [J].
SOUTHERN, EM .
JOURNAL OF MOLECULAR BIOLOGY, 1975, 98 (03) :503-+
[46]   INTRAPERITONEAL LYMPHOKINE-ACTIVATED KILLER-CELL AND INTERLEUKIN-2 THERAPY FOR MALIGNANCIES LIMITED TO THE PERITONEAL-CAVITY [J].
STEIS, RG ;
URBA, WJ ;
VANDERMOLEN, LA ;
BOOKMAN, MA ;
SMITH, JW ;
CLARK, JW ;
MILLER, RL ;
CRUM, ED ;
BECKNER, SK ;
MCKNIGHT, JE ;
OZOLS, RF ;
STEVENSON, HC ;
YOUNG, RC ;
LONGO, DL .
JOURNAL OF CLINICAL ONCOLOGY, 1990, 8 (10) :1618-1629
[47]  
STEWART JA, 1990, CANCER RES, V50, P6302
[48]   INDUCTION OF THE INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN BY TRANSFORMING GROWTH-FACTOR-BETA [J].
TURNER, M ;
CHANTRY, D ;
KATSIKIS, P ;
BERGER, A ;
BRENNAN, FM ;
FELDMANN, M .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1991, 21 (07) :1635-1639
[49]   INTRAPERITONEAL LYMPHOKINE-ACTIVATED KILLER CELL INTERLEUKIN-2 THERAPY IN PATIENTS WITH INTRA-ABDOMINAL CANCER - IMMUNOLOGICAL CONSIDERATIONS [J].
URBA, WJ ;
CLARK, JW ;
STEIS, RG ;
BOOKMAN, MA ;
SMITH, JW ;
BECKNER, S ;
MALUISH, AE ;
ROSSIO, JL ;
RAGER, H ;
ORTALDO, JR ;
LONGO, DL .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1989, 81 (08) :602-611
[50]   ISOLATION AND EXPRESSION OF HUMAN CYTOKINE SYNTHESIS INHIBITORY FACTOR CDNA CLONES - HOMOLOGY TO EPSTEIN-BARR-VIRUS OPEN READING FRAME BCRFI [J].
VIEIRA, P ;
DEWAALMALEFYT, R ;
DANG, MN ;
JOHNSON, KE ;
KASTELEIN, R ;
FIORENTINO, DF ;
DEVRIES, JE ;
RONCAROLO, MG ;
MOSMANN, TR ;
MOORE, KW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (04) :1172-1176