New hormone receptor-positive breast cancer mouse cell line mimicking the immune microenvironment of anti-PD-1 resistant mammary carcinoma - Sorbonne Université Access content directly
Journal Articles Journal for Immunotherapy of Cancer Year : 2023

New hormone receptor-positive breast cancer mouse cell line mimicking the immune microenvironment of anti-PD-1 resistant mammary carcinoma

Maria Perez-Lanzon
  • Function : Author
Vincent Carbonnier
  • Function : Author
Pierre Cordier
  • Function : Author
Fatima Domenica Elisa de Palma
  • Function : Author
Adriana Petrazzuolo
  • Function : Author
Floriane Arbaretaz
  • Function : Author
Khady Mangane
  • Function : Author
Gautier Stoll
  • Function : Author
Isabelle Martins
  • Function : Author
Helene Fohrer Ting
  • Function : Author
Juliette Paillet
  • Function : Author
Sophie Mouillet-Richard
  • Function : Author
Delphine Le Corre
  • Function : Author
Wenjjin Xiao
  • Function : Author
Marine Sroussi
  • Function : Author
Chantal Desdouets
  • Function : Author
Pierre Laurent-Puig
  • Function : Author
Carlos Lopez-Otin
  • Function : Author
Maria Chiara Maiuri
Guido Kroemer

Abstract

Background Progress in breast cancer (BC) research relies on the availability of suitable cell lines that can be implanted in immunocompetent laboratory mice. The best studied mouse strain, C57BL/6, is also the only one for which multiple genetic variants are available to facilitate the exploration of the cancer-immunity dialog. Driven by the fact that no hormone receptor-positive (HR + ) C57BL/6-derived mammary carcinoma cell lines are available, we decided to establish such cell lines. Methods BC was induced in female C57BL/6 mice using a synthetic progesterone analog (medroxyprogesterone acetate, MPA) combined with a DNA damaging agent (7,12-dimethylbenz[a]anthracene, DMBA). Cell lines were established from these tumors and selected for dual (estrogen+progesterone) receptor positivity, as well as transplantability into C57BL/6 immunocompetent females. Results One cell line, which we called B6BC, fulfilled these criteria and allowed for the establishment of invasive estrogen receptor-positive (ER + ) tumors with features of epithelial to mesenchymal transition that were abundantly infiltrated by myeloid immune populations but scarcely by T lymphocytes, as determined by single-nucleus RNA sequencing and high-dimensional leukocyte profiling. Such tumors failed to respond to programmed cell death-1 (PD-1) blockade, but reduced their growth on treatment with ER antagonists, as well as with anthracycline-based chemotherapy, which was not influenced by T-cell depletion. Moreover, B6BC-derived tumors reduced their growth on CD11b blockade, indicating tumor sustainment by myeloid cells. The immune environment and treatment responses recapitulated by B6BC-derived tumors diverged from those of ER + TS/A cell-derived tumors in BALB/C mice, and of ER – E0771 cell-derived and MPA/DMBA-induced tumors in C57BL/6 mice. Conclusions B6BC is the first transplantable HR + BC cell line derived from C57BL/6 mice and B6BC-derived tumors recapitulate the complex tumor microenvironment of locally advanced HR + BC naturally resistant to PD-1 immunotherapy.

Dates and versions

hal-04210300 , version 1 (18-09-2023)

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Maria Perez-Lanzon, Vincent Carbonnier, Pierre Cordier, Fatima Domenica Elisa de Palma, Adriana Petrazzuolo, et al.. New hormone receptor-positive breast cancer mouse cell line mimicking the immune microenvironment of anti-PD-1 resistant mammary carcinoma. Journal for Immunotherapy of Cancer, 2023, 11 (6), pp.e007117. ⟨10.1136/jitc-2023-007117⟩. ⟨hal-04210300⟩
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