IL-4-transduced tumor cell vaccine induces immunoregulatory type 2 CD8 T lymphocytes that cure lung metastases upon adoptive transfer

Monica Rodolfo, Chiara Zilocchi, Paola Accornero, Barbara Cappetti, Ivano Arioli, Mario P. Colombo

Research output: Contribution to journalArticle

Abstract

Vaccinations with tumor cells engineered to produce IL-4 prolonged survival and cured 30% of mice bearing pulmonary metastases, an effect abrogated by in vivo depletion of T cells. Vaccination induced type 2 T cell polarization in both CD4 and CD8 T lymphocyte subsets. We focused on the antitumor activity exerted by type 2 CD8+ T cells (Tc2) activated by IL-4 tumor cell vaccination. Tc2 lymphocytes lacked in vitro tumor cytotoxicity, but released IL-4 upon stimulation with tumor cells, as shown by limiting dilution analysis of the frequencies of tumor-specific pCTL and of CD8 cells producing the cytokine. In vivo fresh purified CD8+ T lymphocytes from IL- 4-vaccinated mice eliminated 80-100% of lung metastases when transferred into tumor-bearing mice. CD8+ lymphocytes from IL-4-vaccinated IFN-γ knockout (KO), but not from IL-4 KO, mice cured lung metastases, thus indicating that IL-4 produced by Tc2 cells was instrumental for tumor rejection. The antitumor effect of adoptively transferred Tc2 lymphocytes needed host CD8 T cells and AsGM1 leukocyte populations, and partially granulocytes. These data indicate that Tc2 CD8+ T cells exert immunoregulatory functions and induce tumor rejection through the cooperation of bystander lymphoid effector cells. Tumor eradication is thus not restricted to a type 1 response, but can also be mediated by a type 2 biased T cell response.

Original languageEnglish
Pages (from-to)1923-1928
Number of pages6
JournalJournal of Immunology
Volume163
Issue number4
Publication statusPublished - Aug 15 1999

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Cancer Vaccines
Adoptive Transfer
Interleukin-4
Neoplasm Metastasis
T-Lymphocytes
Lung
Neoplasms
Lymphocytes
Vaccination
T-Lymphocyte Subsets
Granulocytes
Knockout Mice
Leukocytes
Cytokines

ASJC Scopus subject areas

  • Immunology

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IL-4-transduced tumor cell vaccine induces immunoregulatory type 2 CD8 T lymphocytes that cure lung metastases upon adoptive transfer. / Rodolfo, Monica; Zilocchi, Chiara; Accornero, Paola; Cappetti, Barbara; Arioli, Ivano; Colombo, Mario P.

In: Journal of Immunology, Vol. 163, No. 4, 15.08.1999, p. 1923-1928.

Research output: Contribution to journalArticle

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AU - Arioli, Ivano

AU - Colombo, Mario P.

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