Reprogramming tumor-infiltrating dendritic cells for CD103+CD8+ Mucosal T-cell differentiation and breast cancer rejection

Te Chia Wu, Kangling Xu, Romain Banchereau, Florentina Marches, Chun I. Yu, Jan Martinek, Esperanza Anguiano, Alexander Pedroza-Gonzalez, G. Jackson Snipes, Joyce O'Shaughnessy, Stephen Nishimura, Yong Jun Liu, Virginia Pascual, Jacques Banchereau, Sangkon Oh, Karolina Palucka

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Our studies showed that tumor-infiltrating dendritic cells (DC) in breast cancer drive inflammatory Th2 (iTh2) cells and protumor inflammation. Here, we show that intratumoral delivery of the b-glucan curdlan, a ligand of dectin-1, blocks the generation of iTh2 cells and prevents breast cancer progression in vivo. Curdlan reprograms tumor-infiltrating DCs via the ligation of dectin-1, enabling the DCs to become resistant to cancer-derived thymic stromal lymphopoietin (TSLP), to produce IL-12p70, and to favor the generation of Th1 cells. DCs activated via dectin-1, but not those activated with TLR-7/8 ligand or poly:C, induce CD8+ T cells to express CD13 (αE integrin), a ligand for cancer cells, E-cadherin. Generation of these mucosal CD8+ T cells is regulated by DC-derived integrin αvβ8 and TGF-β activation in a dectin-1-dependent fashion. These CD103+CD8+ mucosal T cells accumulate in the tumors, thereby increasing cancer necrosis and inhibiting cancer progression in vivo in a humanized mouse model of breast cancer. Importantly, CD103+ CD8+ mucosal T cells elicited by reprogrammed DCs can reject established cancer. Thus, reprogramming tumor-infiltrating DCs represents a new strategy for cancer rejection.

Original languageEnglish (US)
Pages (from-to)487-500
Number of pages14
JournalCancer Immunology Research
Volume2
Issue number5
DOIs
StatePublished - May 2014

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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    Wu, T. C., Xu, K., Banchereau, R., Marches, F., Yu, C. I., Martinek, J., Anguiano, E., Pedroza-Gonzalez, A., Snipes, G. J., O'Shaughnessy, J., Nishimura, S., Liu, Y. J., Pascual, V., Banchereau, J., Oh, S., & Palucka, K. (2014). Reprogramming tumor-infiltrating dendritic cells for CD103+CD8+ Mucosal T-cell differentiation and breast cancer rejection. Cancer Immunology Research, 2(5), 487-500. https://doi.org/10.1158/2326-6066.CIR-13-0217