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Memory type 2 helper T cells induce long-lasting antitumor immunity by activating natural killer cells
- Publication Year :
- 2011
- Publisher :
- US : American Association for Cancer Research, 2011.
-
Abstract
- Functionally polarized helper T cells (Th cells) play crucial roles in the induction of tumor immunity. There is considerable knowledge about the contributions of IFN-producing Th1 cells that supports the role of cytotoxic cluster of differentiation (CD8) T cells and natural killer (NK) cells, but much less is known about how IL-4–producing Th2 cells contribute to tumor immunity. In this study, we investigated the cellular and molecular mechanisms employed by memory Th2 cells in sustaining tumor immunity by using a mouse model system wherein ovalbumin (OVA) is used as a specific tumor antigen. In this model, we found that OVA-specific memory Th2 cells exerted potent and long-lasting antitumor effects against NK-sensitive OVA-expressing tumor cells, wherein antitumor effects were mediated by NK cells. Specifically, NK cell cytotoxic activity and expression of perforin and granzyme B were dramatically enhanced by the activation of memory Th2 cells. Interleukin 4 (IL-4) produced by memory Th2 cells in vivo was critical for the antitumor effects of the NK cells, which IL-4 directly stimulated to induce their perforin- and granzyme-B–dependent cytotoxic activity. Our findings show that memory Th2 cells can induce potent antitumor immunity through IL-4–induced activation of NK cells, suggesting potential applications in cellular therapy for cancer patients. Cancer Res; 71(14); 4790–8. ©2011 AACR.
- Subjects :
- Cytotoxicity, Immunologic
Cancer Research
Mice, Nude
Mice, Transgenic
Cell Growth Processes
Lymphocyte Activation
Immunotherapy, Adoptive
Cell therapy
killer cells
Interleukin 21
Mice
Lymphocytes, Tumor-Infiltrating
Th2 Cells
Cytotoxic T cell
Animals
Interleukin 4
natural
Mice, Inbred BALB C
immunologic memory
biology
Chemistry
Histone-Lysine N-Methyltransferase
Neoplasms, Experimental
Natural killer T cell
Granzyme B
Killer Cells, Natural
Mice, Inbred C57BL
Th2 cells
Oncology
Perforin
biology.protein
Cancer research
Interleukin 12
Interleukin-4
Immunologic Memory
Myeloid-Lymphoid Leukemia Protein
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....c14754b45e062780a7b9b87f54baec35