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Comparative immune profiling of an aggressive 4T1-based versus a non-aggressive Py230-based intraductal model for triple-negative breast cancer

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Abstract
The intraductal model for breast cancer allows to investigate the human disease process from early ductal carcinoma in situ (DCIS) to late-stage invasive carcinoma (IC). However, detailed knowledge on the immunological changes associated with intraductal tumor growth is currently lacking. Our study aimed to characterize the tumor microenvironment upon DCIS to IC progression in the immunocompetent intraductal model, focusing on triple-negative breast cancer (TNBC). Therefore, BALB/c-derived 4T1 and C57BL/6-derived Py230 mammary tumor cell lines were intraductally inoculated in a syngeneic background and tumor growth was monitored weekly for 6 weeks. The 4T1 cells grew aggressively and invaded the ductal barrier more rapidly than the less invasive Py230 cells. The aggressive tumor progression in the 4T1-based model was accompanied by enhanced production of two immune-related biomarkers chitinase 3-like 1 and lipocalin 2 as well as by more severe splenomegaly compared to the Py230-based model. Flow cytometric and immunohistochemical analysis identified that the ductal breakthrough of both mammary tumor cell lines was associated with primary tumor infiltration of immune cells, including macrophages, neutrophils and T-cells. Furthermore, 4T1 primary tumors showed a more inflammatory and active tumor immune microenvironment based on cytokine profiles and the expression of granzyme B (biomarker for active cytotoxic T-cells) compared to Py230 primary tumors. Our results compared for the first time the immunological changes associated with aggressive versus non-aggressive triple-negative mammary tumor progression in the intraductal TNBC model, providing key information for its future use as immunotherapeutic screening tool.

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Chicago
Steenbrugge, Jonas, Niels Vander Elst, Kristel Demeyere, Olivier De Wever, Steven Van Laere, and Evelyne Meyer. 2019. “Comparative Immune Profiling of an Aggressive 4T1-based Versus a Non-aggressive Py230-based Intraductal Model for Triple-negative Breast Cancer.” In Defence Is the Best Attack: Immuno-oncology Breakthroughs, 2nd EACR Conference, Abstracts.
APA
Steenbrugge, J., Vander Elst, N., Demeyere, K., De Wever, O., Van Laere, S., & Meyer, E. (2019). Comparative immune profiling of an aggressive 4T1-based versus a non-aggressive Py230-based intraductal model for triple-negative breast cancer. Defence is the best attack: immuno-oncology breakthroughs, 2nd EACR conference, Abstracts. Presented at the 2nd EACR conference Defence is the best attck: immuno-oncology breakthroughs.
Vancouver
1.
Steenbrugge J, Vander Elst N, Demeyere K, De Wever O, Van Laere S, Meyer E. Comparative immune profiling of an aggressive 4T1-based versus a non-aggressive Py230-based intraductal model for triple-negative breast cancer. Defence is the best attack: immuno-oncology breakthroughs, 2nd EACR conference, Abstracts. 2019.
MLA
Steenbrugge, Jonas et al. “Comparative Immune Profiling of an Aggressive 4T1-based Versus a Non-aggressive Py230-based Intraductal Model for Triple-negative Breast Cancer.” Defence Is the Best Attack: Immuno-oncology Breakthroughs, 2nd EACR Conference, Abstracts. 2019. Print.
@inproceedings{8627539,
  abstract     = {The intraductal model for breast cancer allows to investigate the human disease process from early ductal carcinoma in situ (DCIS) to late-stage invasive carcinoma (IC). However, detailed knowledge on the immunological changes associated with intraductal tumor growth is currently lacking. Our study aimed to characterize the tumor microenvironment upon DCIS to IC progression in the immunocompetent intraductal model, focusing on triple-negative breast cancer (TNBC). Therefore, BALB/c-derived 4T1 and C57BL/6-derived Py230 mammary tumor cell lines were intraductally inoculated in a syngeneic background and tumor growth was monitored weekly for 6 weeks. The 4T1 cells grew aggressively and invaded the ductal barrier more rapidly than the less invasive Py230 cells. The aggressive tumor progression in the 4T1-based model was accompanied by enhanced production of two immune-related biomarkers chitinase 3-like 1 and lipocalin 2 as well as by more severe splenomegaly compared to the Py230-based model. Flow cytometric and immunohistochemical analysis identified that the ductal breakthrough of both mammary tumor cell lines was associated with primary tumor infiltration of immune cells, including macrophages, neutrophils and T-cells. Furthermore, 4T1 primary tumors showed a more inflammatory and active tumor immune microenvironment based on cytokine profiles and the expression of granzyme B (biomarker for active cytotoxic T-cells) compared to Py230 primary tumors. Our results compared for the first time the immunological changes associated with aggressive versus non-aggressive triple-negative mammary tumor progression in the intraductal TNBC model, providing key information for its future use as immunotherapeutic screening tool.},
  author       = {Steenbrugge, Jonas and Vander Elst, Niels and Demeyere, Kristel and De Wever, Olivier and Van Laere, Steven and Meyer, Evelyne},
  booktitle    = {Defence is the best attack: immuno-oncology breakthroughs, 2nd EACR conference, Abstracts},
  location     = {Barcelona, Spain},
  title        = {Comparative immune profiling of an aggressive 4T1-based versus a non-aggressive Py230-based intraductal model for triple-negative breast cancer},
  year         = {2019},
}