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Updated: Jul 3, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Identification of CD160-TM as a tumor target on triple negative breast cancers: possible therapeutic applications
Claire Scheffges1,2,3, Jérôme Devy4, Jérôme Giustiniani5
1INSERM U976, HIPI, Team 1, 75010, Paris, France.
Background:
Despite major therapeutic advances, triple-negative breast cancer (TNBC) still presents a worth prognosis than hormone receptors-positive breast cancers. One major issue relies in the molecular and mutational heterogeneity of TNBC subtypes that is reinforced by the absence of reliable tumor-antigen that could serve as a specific target to further promote efficient tumor cell recognition and depletion. CD160 is a receptor mainly expressed by NK lymphocytes and presenting two isoforms, namely the GPI-anchored form (CD160-GPI) and the transmembrane isoform (CD160-TM). While CD160-GPI is constitutively expressed on resting cells and involved in the generation of NK cells' cytotoxic activity, CD160-TM is neo-synthesized upon activation and promotes the amplification of NK cells' killing ability.
Methods:
CD160 expression was assessed by immunohistochemistry (IHC) and flow cytometry on TNBC patient biopsies or cell lines, respectively. Antibody (Ab)-mediated tumor depletion was tested in vitro by performing antibody-dependent cell cytotoxicity (ADCC) and phagocytosis (ADCP) assays, and in vivo on a TNBC mouse model.
Results:
Preliminary data obtained by IHC on TNBC patients' tumor biopsies revealed an unconventional expression of CD160 by TNBC tumor cells. By using a specific but conformation-dependent anti-CD160-TM Ab, we established that CD160-TM, but not CD160-GPI, was expressed by TNBC tumor cells. A conformation-independent anti-CD160-TM mAb (22B12; muIgG2a isotype) was generated and selected according to pre-defined specificity and functional criterions. In vitro functional assays demonstrated that ADCC and ADCP could be induced in the presence of 22B12, resulting in TNBC cell line apoptosis. The ability of 22B12 to exert an in vivo anti-tumor activity was also demonstrated on a TNBC murine model.
Conclusions:
Our data identify CD160-TM as a tumor marker for TNBC and provide a rational for the use of anti-CD160-TM antibodies as therapeutic tools in this tumor context.
Insights
Triple-negative breast cancer (TNBC) cells express CD160 transmembrane isoform (CD160-TM), a potential therapeutic target. Antibodies targeting CD160-TM demonstrated anti-tumor activity in vitro and in vivo, offering a new treatment strategy for TNBC.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) has a poorer prognosis than hormone receptor-positive breast cancers due to its heterogeneity and lack of specific tumor targets.
- CD160 is a receptor expressed on NK lymphocytes, with two isoforms: CD160-GPI and CD160-TM.
- CD160-GPI is constitutively expressed and involved in NK cell cytotoxicity, while CD160-TM is neo-synthesized upon activation to enhance killing ability.
Purpose of the Study:
- To investigate CD160 expression in TNBC tumor cells.
- To evaluate the therapeutic potential of targeting CD160-TM in TNBC.
Main Methods:
- Immunohistochemistry (IHC) and flow cytometry were used to assess CD160 expression on TNBC patient biopsies and cell lines.
- In vitro antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cell phagocytosis (ADCP) assays were performed.
- In vivo anti-tumor activity was evaluated using a TNBC mouse model.
Main Results:
- TNBC tumor cells were found to express CD160-TM, but not CD160-GPI.
- A novel conformation-independent anti-CD160-TM monoclonal antibody (mAb), 22B12, was generated.
- Treatment with 22B12 induced apoptosis in TNBC cell lines via ADCC and ADCP in vitro and demonstrated anti-tumor activity in vivo.
Conclusions:
- CD160-TM is identified as a tumor marker for TNBC.
- Anti-CD160-TM antibodies, such as 22B12, represent a promising therapeutic strategy for TNBC.
