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Editorial
. 2023 Aug 3;12(1):2240613.
doi: 10.1080/2162402X.2023.2240613. eCollection 2023.

Mammary carcinoma: toward a realistic mouse model of incurable cancers

Maria Pérez-Lanzón  1   2 , Maria Chiara Maiuri  1   2   3 , Carlos Lopez-Otin  4 , Guido Kroemer  1   2   5
Affiliations
Editorial

Mammary carcinoma: toward a realistic mouse model of incurable cancers

Maria Pérez-Lanzón et al. Oncoimmunology. .

Abstract

As long as breast cancer (BC) stays under immunosurveillance, it can be controlled by treatments eliciting anticancer immune responses. However, once BC escapes immunosurveillance, it becomes therapeutically uncontrollable. A paper in the Journal for ImmunoTherapy of Cancer describes a new hormone receptor-positive BC cell line generating incurable tumors in C57BL/6 mice.

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Conflict of interest statement

GK has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Tollys, and Vascage. GK is on the Board of Directors of the Bristol Myers Squibb Foundation France. GK is a scientific co-founder of EverImmune, Osasuna Therapeutics, Samsara Therapeutics, and Therafast Bio. GK is on the scientific advisory boards of Hevolution, Institut Servier, and Longevity Vision Funds. GK is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis, and metabolic disorders. GK’s wife, Laurence Zitvogel, has held research contracts with Glaxo Smyth Kline, Incyte, Lytix, Kaleido, Innovate Pharma, Daiichi Sankyo, Pilege, Merus, Transgene, 9m, Tusk, and Roche, was on the Board of Directors of Transgene, is a cofounder of everImmune, and holds patents covering the treatment of cancer and the therapeutic manipulation of the microbiota. GK’s brother, Romano Kroemer, was an employee of Sanofi and now consults for Boehringer-Ingelheim. The funders had no role in the design of the study; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1.
Figure 1.
Schematic representation of the principles of cancer immunosurveillance and the generation of B6BC transplantable tumor (TT). (a) Principles of immunosurveillance in the context of hormone receptor-positive (HR+) breast cancer (BC). BCs induced by the progesterone analogue medroxyprogesterone acetate (MPA) combined with the DNA damaging agent 7,12-dimethylbenz[a]anthracene (DMBA) develop with a delay in immunocompetent C57BL/6 mice as compared to severe immunodeficient mice lacking T and NK cells (phenotype Rag2−/− Il2rg-/-), reflecting T and NK cell-mediated immunoediting. Of note, animals lacking functional T cells (phenotype Rag2−/− or depleted of CD4+ and CD8+ cells) show a similar tumor latency to C57BL/6 mice. Transplantation of tumor-derived cell lines from immunocompetent to immunodeficient is possible but not vice versa. Moreover, the dose (high = 5 × 106 cells or low = 5 × 105 cells) and the way of generation of the cancer cells that are transferred (MGT cells or BXBC cells among which B6BC cells), influence transplantability of tumors among immunocompetent mice. (b) Molecular differences between original (OT) and transplanted (TT) B6BC cancers generated by the injection of very low doses of B6BC cells (2 × 105 cells), as determined by histopathological, immunological and single nucleus RNA sequencing analyses. Figure created with Biorender.com.
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References

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Publication types

Grants and funding

GK is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; Fondation pour la Recherche Médicale (FRM); a donation by Elior; Equipex Onco-Pheno-Screen; European Joint Programme on Rare Diseases (EJPRD); European Research Council Advanced Investigator Award (ERC-2021-ADG, ICD-Cancer, Grant No. 101052444), European Union Horizon 2020 Projects Oncobiome, Prevalung (grant No. 101095604) and Crimson; Fondation Carrefour; Institut National du Cancer (INCa); Institut Universitaire de France; LabEx Immuno-Oncology (ANR-18-IDEX-0001); a Cancer Research ASPIRE Award from the Mark Foundation; the RHU Immunolife; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and SIRIC Cancer Research and Personalized Medicine (CARPEM). This study contributes to the IdEx Université de Paris ANR-18-IDEX-0001.