title: Analysis of host versus tumor interaction in cancer patients: opposing role of transforming growth factor-beta1 and interleukin-6 in the development of in situ tumor immunity.
abstract: A different degree of immunodeficiency is often found at tumor sites in cancer patients. At the late stage many patients develop malignant effusion that contains large numbers of tumor cells and host immune cells that constantly interact with each other. These sites may provide an ideal model to examine in situ anti-tumor immunity. The T cells in effusion were found to be immunodeficient, which suggested a defective anti-tumor cytotoxic T lymphocytes response. To pursue the mechanism for the T cell deficiency, we determined the production of immunomodulating cytokines in the effusion and detected the presence of transforming growth factor-beta1 (TGFbeta), prostaglandin E2, IL-6, IL-10, and IFNgamma. There was no detectable IL-2, IL-4, IL-12, or TNFalpha. The most prominent feature was the presence of TGFbeta and IL-6 at a very high level. Thus, the possible role of these two cytokines on T cell competence was further determined. TGFbeta was found to induce T cell anergy and reduced the production of perforin in T killer cells and their lytic activity. These events lead to the induction of peripheral T cell tolerance with profound T cell deficiency. IL-6 did not affect perforin production or cytolytic activity of the T killer cells. But the CD4+ CD25+ regulatory T cells (TR) that were often employed by TGFbeta to suppress T cell response were reduced in the malignant effusion, consistent with the fact that IL-6 down-regulates TR and this may represent the host's vigorous response to the tumor's subversion. These results show that TGFbeta and IL-6 might play pivotal but opposing roles in the host tumor interaction that, together with other immunomodulating components, determines the outcome for the development of local tumor immunity.
authors.affiliation: Immunology Group, National Health Research Institutes, Taipei, Taiwan.
authors.forename: Jy-Ping
authors.initials: JP
authors.lastname: Tsai
authors.forename: Hsin-Wei
authors.initials: HW
authors.lastname: Chen
authors.forename: Mei-Lien
authors.initials: ML
authors.lastname: Cheng
authors.forename: Hsiung-Kun
authors.initials: HK
authors.lastname: Liu
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Lee
authors.forename: Chia Ling
authors.initials: CL
authors.lastname: Hsieh
authors.forename: Kwen-Tay
authors.initials: KT
authors.lastname: Luh
authors.forename: Chew-Wun
authors.initials: CW
authors.lastname: Wu
authors.forename: Li-Han
authors.initials: LH
authors.lastname: Hsu
authors.forename: Tsu-Yi
authors.initials: TY
authors.lastname: Chao
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Wang
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Chang
authors.forename: Chou-Chik
authors.initials: CC
authors.lastname: Ting
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007121:Immunocompetence; D007165:Immunosuppression Therapy; D015850:Interleukin-6 / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
chemical_list: D015850:Interleukin-6; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D054353:Perforin