HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sheu, B.-C. Articles by Huang, S.-C. Search for Related Content PubMed PubMed Citation Articles by Sheu, B.-C. Articles by Huang, S.-C.

Predominant Th2/Tc2 Polarity of Tumor-Infiltrating Lymphocytes in Human Cervical Cancer¹

Bor-Ching Sheu^*, Rong-Hwa Lin, Huang-Chun Lien, Hong-Nerng Ho^*,, Su-Ming Hsu^, and Su-Cheng Huang^2,*

Departments of ^* Obstetrics and Gynecology and Pathology, National Taiwan University Hospital, and Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan

Cytotoxic T lymphocytes (Tc) play a central role in cellular immunity against cancers. The cytotoxic potential of freshly isolated tumor-infiltrating lymphocytes (TILs) is usually not expressed. This suggests the possible existence of as yet unspecified and perhaps complex immunosuppressive factors or cytokines that affect the anti-tumor capacity of these TILs in the tumor milieu. In the present study, we demonstrated for the first time that TILs derived from human cervical cancer tissue consist mainly of Th2/Tc2 phenotypes. In vitro kinetic assays further revealed that cancer cells could direct the tumor-encountered T cells toward the Th2/Tc2 polarity. Cancer cells promote the production of IL-4 and down-regulate the production of IFN- in cancer-encountered T cells. The regulatory effects of cervical cancer cells are mediated mainly by IL-10, and TGF- plays only a synergistic role. The cancer-derived effects can be reversed by neutralizing anti-IL-10 and anti-TGF- Abs. IL-10 and TGF- are present in cancer tissue and weakly expressed in precancerous tissue, but not in normal cervical epithelial cells. Our study strongly suggests important regulatory roles of IL-10 and TGF- in cancer-mediated immunosuppression.

This article has been cited by other articles:

				S.-J. Liu, J.-P. Tsai, C.-R. Shen, Y.-P. Sher, C.-L. Hsieh, Y.-C. Yeh, A.-H. Chou, S.-R. Chang, K.-N. Hsiao, F.-W. Yu, et al. Induction of a distinct CD8 Tnc17 subset by transforming growth factor-{beta} and interleukin-6 J. Leukoc. Biol., August 1, 2007; 82(2): 354 - 360. [Abstract] [Full Text] [PDF]

				M. J. Dobrzanski, J. B. Reome, J. C. Hylind, and K. A. Rewers-Felkins CD8-Mediated Type 1 Antitumor Responses Selectively Modulate Endogenous Differentiated and Nondifferentiated T Cell Localization, Activation, and Function in Progressive Breast Cancer J. Immunol., December 1, 2006; 177(11): 8191 - 8201. [Abstract] [Full Text] [PDF]

				A. Bot, D. Smith, B. Phillips, S. Bot, C. Bona, and H. Zaghouani Immunologic Control of Tumors by In Vivo Fc{gamma} Receptor-Targeted Antigen Loading in Conjunction with Double-Stranded RNA-Mediated Immune Modulation J. Immunol., February 1, 2006; 176(3): 1363 - 1374. [Abstract] [Full Text] [PDF]

				S. Olver, P. Groves, K. Buttigieg, E. S. Morris, M. L. Janas, A. Kelso, and N. Kienzle Tumor-Derived Interleukin-4 Reduces Tumor Clearance and Deviates the Cytokine and Granzyme Profile of Tumor-Induced CD8+ T Cells Cancer Res., January 1, 2006; 66(1): 571 - 580. [Abstract] [Full Text] [PDF]

				J. N. Kloth, G. J. Fleuren, J. Oosting, R. X. de Menezes, P. H.C. Eilers, G. G. Kenter, and A. Gorter Substantial changes in gene expression of Wnt, MAPK and TNF{alpha} pathways induced by TGF-{beta}1 in cervical cancer cell lines Carcinogenesis, September 1, 2005; 26(9): 1493 - 1502. [Abstract] [Full Text] [PDF]

				B.-C. Sheu, S.-H. Chiou, H.-H. Lin, S.-N. Chow, S.-C. Huang, H.-N. Ho, and S.-M. Hsu Up-regulation of Inhibitory Natural Killer Receptors CD94/NKG2A with Suppressed Intracellular Perforin Expression of Tumor-Infiltrating CD8+ T Lymphocytes in Human Cervical Carcinoma Cancer Res., April 1, 2005; 65(7): 2921 - 2929. [Abstract] [Full Text] [PDF]

				A. de Jong, M. I. E. van Poelgeest, J. M. van der Hulst, J. W. Drijfhout, G. J. Fleuren, C. J. M. Melief, G. Kenter, R. Offringa, and S. H. van der Burg Human Papillomavirus Type 16-Positive Cervical Cancer Is Associated with Impaired CD4+ T-Cell Immunity against Early Antigens E2 and E6 Cancer Res., August 1, 2004; 64(15): 5449 - 5455. [Abstract] [Full Text] [PDF]

				J. A. DeVoti, B. M. Steinberg, D. W. Rosenthal, L. Hatam, A. Vambutas, A. L. Abramson, M. J. Shikowitz, and V. R. Bonagura Failure of Gamma Interferon but Not Interleukin-10 Expression in Response to Human Papillomavirus Type 11 E6 Protein in Respiratory Papillomatosis Clin. Vaccine Immunol., May 1, 2004; 11(3): 538 - 547. [Abstract] [Full Text] [PDF]

				M. J. Dobrzanski, J. B. Reome, J. A. Hollenbaugh, and R. W. Dutton Tc1 and Tc2 Effector Cell Therapy Elicit Long-Term Tumor Immunity by Contrasting Mechanisms That Result in Complementary Endogenous Type 1 Antitumor Responses J. Immunol., February 1, 2004; 172(3): 1380 - 1390. [Abstract] [Full Text] [PDF]

				K.-H. Chao, M.-Y. Wu, J.-H. Yang, S.-U. Chen, Y.-S. Yang, and H.-N. Ho Expression of the interleukin-2 receptor {alpha} (CD25) is selectively decreased on decidual CD4+ and CD8+ T lymphocytes in normal pregnancies Mol. Hum. Reprod., July 1, 2002; 8(7): 667 - 673. [Abstract] [Full Text] [PDF]