Dendritic cells (DCs) induce, sustain and regulate immune responses. We have observed an abundant infiltration of breast cancer (BrCa) tissue with DCs and a striking compartmentalization with immature DCs residing within the tumor (32/32 samples) and mature DCs in tumor stroma (20/32 samples). The presence of mature DCs is puzzling as they are normally found only in secondary lymphoid organs where they initiate and sustain activation and expansion of antigen-specific T cells. We wish to analyze the role and function of tumor infiltrating DCs with the concept that the presence of mature DCs at tumor site indicates tumor-specific immunity.
Our specific aims are as follows: To determine whether DCs loaded with killed breast cancer cells can prime na?ve T cells to differentiate into breast cancer-specific CTL. These lines will be used to test whether breast tumor- associated DCs express BrCa antigens. Furthermore they may permit us to identify in vitro tumor rejection antigens, and, eventually novel breast cancer antigens. To determine whether mature breast tumor-associated DsC present breast cancer antigens. We will conclude whether infiltration of breast tumors with mature DCs reflects an ongoing breast tumor specific immune response. To determine whether immature breast tumor-associated DCs capture and then present breast cancer antigens. We will conclude whether lack of mature DCs infiltration in breast tumor tissue reflects dysfunction of immature DCs and lack of breast tumor specific immune responses. Here we propose a novel approach to understand the development of BrCa-specific immunity. Overall, this proposal will permit us to demonstrate that efficient breast cancer immunity can be generated and used to reject the tumor thus permitting development of novel treatment modalities in breast cancer.
| Wu, Te-Chia; Xu, Kangling; Banchereau, Romain et al. (2014) Reprogramming tumor-infiltrating dendritic cells for CD103+ CD8+ mucosal T-cell differentiation and breast cancer rejection. Cancer Immunol Res 2:487-500 |
| Palucka, Karolina; Banchereau, Jacques (2013) Human dendritic cell subsets in vaccination. Curr Opin Immunol 25:396-402 |
| Palucka, Karolina; Banchereau, Jacques (2013) Dendritic-cell-based therapeutic cancer vaccines. Immunity 39:38-48 |
| Palucka, Karolina; Banchereau, Jacques (2012) Cancer immunotherapy via dendritic cells. Nat Rev Cancer 12:265-77 |
| Palucka, Karolina; Ueno, Hideki; Roberts, Lee et al. (2011) Dendritic cell subsets as vectors and targets for improved cancer therapy. Curr Top Microbiol Immunol 344:173-92 |
| Palucka, K; Ueno, H; Fay, J et al. (2011) Dendritic cells and immunity against cancer. J Intern Med 269:64-73 |
| Pedroza-Gonzalez, Alexander; Xu, Kangling; Wu, Te-Chia et al. (2011) Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation. J Exp Med 208:479-90 |
| Palucka, Karolina; Ueno, Hideki; Banchereau, Jacques (2011) Recent developments in cancer vaccines. J Immunol 186:1325-31 |
| Ueno, Hideki; Klechevsky, Eynav; Schmitt, Nathalie et al. (2011) Targeting human dendritic cell subsets for improved vaccines. Semin Immunol 23:21-7 |
| Palucka, Karolina; Banchereau, Jacques; Mellman, Ira (2010) Designing vaccines based on biology of human dendritic cell subsets. Immunity 33:464-78 |
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