Tumor-induced CD11b+Gr-1+ myeloid cells suppress T cell sensitization in tumor-draining lymph nodes

Satoshi Watanabe, Katsuya Deguchi, Rongxiu Zheng, Hidemasa Tamai, Li Xin Wang, Peter A Cohen, Suyu Shu

Research output: Contribution to journalArticle

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Abstract

Suppression of tumor-specific T cell sensitization is a predominant mechanism of tumor escape. To identify tumor-induced suppressor cells, we transferred spleen cells from mice bearing progressive MCA205 sarcoma into sublethally irradiated mice. These mice were then inoculated subdermally with tumor cells to stimulate T cell response in the tumor-draining lymph-node (TDLN). Tumor progression induced splenomegaly with a dramatic increase (22.1%) in CD11b+Gr-1+ myeloid-derived suppressor cells (MDSC) compared with 2.6% of that in normal mice. Analyses of therapeutic effects by the adoptive immunotherapy revealed that the transfer of spleen cells from tumor-bearing mice severely inhibited the generation of tumor-immune T cells in the TDLN. We further identified MDSC to be the dominant suppressor cells. However, cells of identical phenotype from normal spleens lacked the suppressive effects. The suppression was independent of CD4+CD25+ regulatory T cells. Intracellular IFN-γ staining revealed that the transfer of MDSC resulted in a decrease in numbers of tumor-specific CD4 + and CD8+ T cells. Transfer of MDSC from MCA207 tumor-bearing mice also suppressed the MCA205 immune response indicating a lack of immunologic specificity. Further analyses demonstrated that MDSC inhibited T cell activation that was triggered either by anti-CD3 mAb or by tumor cells. However, MDSC did not suppress the function of immune T cells in vivo at the effector phase. Our data provide the first evidence that the systemic transfer of MDSC inhibited and interfered with the sensitization of tumor-specific T cell responses in the TDLN.

Original languageEnglish (US)
Pages (from-to)3291-3300
Number of pages10
JournalJournal of Immunology
Volume181
Issue number5
StatePublished - Sep 1 2008
Externally publishedYes

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Myeloid Cells
Lymph Nodes
T-Lymphocytes
Neoplasms
Spleen
Tumor Escape
Adoptive Immunotherapy
Splenomegaly
Therapeutic Uses
Regulatory T-Lymphocytes
Myeloid-Derived Suppressor Cells
Sarcoma
Staining and Labeling

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Watanabe, S., Deguchi, K., Zheng, R., Tamai, H., Wang, L. X., Cohen, P. A., & Shu, S. (2008). Tumor-induced CD11b+Gr-1+ myeloid cells suppress T cell sensitization in tumor-draining lymph nodes. Journal of Immunology, 181(5), 3291-3300.

Tumor-induced CD11b+Gr-1+ myeloid cells suppress T cell sensitization in tumor-draining lymph nodes. / Watanabe, Satoshi; Deguchi, Katsuya; Zheng, Rongxiu; Tamai, Hidemasa; Wang, Li Xin; Cohen, Peter A; Shu, Suyu.

In: Journal of Immunology, Vol. 181, No. 5, 01.09.2008, p. 3291-3300.

Research output: Contribution to journalArticle

Watanabe, S, Deguchi, K, Zheng, R, Tamai, H, Wang, LX, Cohen, PA & Shu, S 2008, 'Tumor-induced CD11b+Gr-1+ myeloid cells suppress T cell sensitization in tumor-draining lymph nodes', Journal of Immunology, vol. 181, no. 5, pp. 3291-3300.
Watanabe S, Deguchi K, Zheng R, Tamai H, Wang LX, Cohen PA et al. Tumor-induced CD11b+Gr-1+ myeloid cells suppress T cell sensitization in tumor-draining lymph nodes. Journal of Immunology. 2008 Sep 1;181(5):3291-3300.
Watanabe, Satoshi ; Deguchi, Katsuya ; Zheng, Rongxiu ; Tamai, Hidemasa ; Wang, Li Xin ; Cohen, Peter A ; Shu, Suyu. / Tumor-induced CD11b+Gr-1+ myeloid cells suppress T cell sensitization in tumor-draining lymph nodes. In: Journal of Immunology. 2008 ; Vol. 181, No. 5. pp. 3291-3300.
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