Predominant Th2/Tc2 polarity of tumor-infiltrating lymphocytes in human cervical cancer.
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-gamma in cancer-encountered T cells. The regulatory effects of cervical cancer cells are mediated mainly by IL-10, and TGF-beta plays only a synergistic role. The cancer-derived effects can be reversed by neutralizing anti-IL-10 and anti-TGF-beta Abs. IL-10 and TGF-beta 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-beta in cancer-mediated immunosuppression.
Sheu
B C
BC
Department of Obstetrics and Gynecology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. bcsheu@ha.mc.ntu.edu.tw
Lin
R H
RH
Lien
H C
HC
Ho
H N
HN
Hsu
S M
SM
Huang
S C
SC
D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D009500:Neutralization Tests; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D016207:Cytokines; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10