Characterization of autologous tumor‐specific T‐helper 2 cells in tumor‐infiltrating lymphocytes from a patient with metastatic melanoma

D. D. Kharkevitch, D. Seito, G. C. Balch, T. Maeda, C. M. Balch, K. Itoh

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Human autologous tumor‐specific T‐helper 2 (Th2) cells were investigated in melanoma tumor‐infiltrating lymphocytes (TILs). Both a CD4+ T‐cell line and its 5 potential T‐cell clones established from TILs of a patient with metastatic melanoma produced significant levels of IL‐4, IL‐6, IL‐10 and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in response to autologous, but not any of 12 allogeneic, melanoma cell lines. They also produced IL‐3 and IL‐8 but not IL‐2, IFN‐γ, TNF‐α or TNF‐β in response to autologous tumor cells. Furthermore, they showed autologous melanoma‐specific cytotoxicity only in an 18‐hr 51Cr‐release assay. Specific IL‐4, IL‐6 or IL‐10 production by the CD4+ M73 T‐cell line and its clone was inhibited by anti‐class 11 DR (but not anti‐class 1) MAb, whereas their specific cytotoxicity was inhibited by anti‐class 1 (but not anti‐class 11) MAb. Anti‐CD3 and ‐CD4 MAb (but not anti‐CD8) abrogated both IL‐4, IL6 and IL‐10 production and cytotoxicity, while anti‐IL‐4 antibody did not inhibit cytotoxicity. CD4+ potential T‐cell clones, but not CD8+ clones, that were established from freshly isolated TILs without in vitro sensitization by autologous tumor cells also produced IL‐4, IL‐6 and IL‐10 but not IFN‐γ or tumor necrosis factor (TNF)α in an autologous tumor‐specific fashion. These Th2 cells were neither reactive to EBV‐B cells nor suppressive against CD8+ T‐cell clones. PMA and PHA stimulated these potential T‐cell clones, regardless of their specific lymphokine production, to produce IL‐3, IL‐4, IL‐6, IL‐8, IL‐10, GM‐CSF, TNFα and IFN‐γ. Our results demonstrate the presence of autologous tumor‐specific Th2 cells at the melanoma sites.

Original languageEnglish (US)
Pages (from-to)317-323
Number of pages7
JournalInternational Journal of Cancer
Volume58
Issue number3
DOIs
StatePublished - Aug 1 1994

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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