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A single-cell transcriptomic landscape of innate and adaptive intratumoral immunity in triple negative breast cancer during chemo- and immunotherapies

View ORCID ProfileLaura Carpen, Paolo Falvo, Stefania Orecchioni, Giulia Mitola, Roman Hillje, Saveria Mazzara, Patrizia Mancuso, Stefano Pileri, View ORCID ProfileAlessandro Raveane, View ORCID ProfileFrancesco Bertolini
doi: https://doi.org/10.1101/2021.12.01.470716
Laura Carpen
1Laboratory of Hematology-Oncology, European Institute of Oncology IRCCS, 20141 Milan, Italy
2Human Technopole, 20157, Milan, Italy
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  • ORCID record for Laura Carpen
Paolo Falvo
1Laboratory of Hematology-Oncology, European Institute of Oncology IRCCS, 20141 Milan, Italy
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Stefania Orecchioni
1Laboratory of Hematology-Oncology, European Institute of Oncology IRCCS, 20141 Milan, Italy
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Giulia Mitola
1Laboratory of Hematology-Oncology, European Institute of Oncology IRCCS, 20141 Milan, Italy
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Roman Hillje
3The Hyve, Utrecht, Netherlands
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Saveria Mazzara
4Hematopathology Unit, European Institute of Oncology IRCCS, 20141 Milan, Italy
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Patrizia Mancuso
1Laboratory of Hematology-Oncology, European Institute of Oncology IRCCS, 20141 Milan, Italy
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Stefano Pileri
1Laboratory of Hematology-Oncology, European Institute of Oncology IRCCS, 20141 Milan, Italy
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Alessandro Raveane
1Laboratory of Hematology-Oncology, European Institute of Oncology IRCCS, 20141 Milan, Italy
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  • ORCID record for Alessandro Raveane
Francesco Bertolini
1Laboratory of Hematology-Oncology, European Institute of Oncology IRCCS, 20141 Milan, Italy
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  • ORCID record for Francesco Bertolini
  • For correspondence: francesco.bertolini@ieo.it
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Abstract

Breast cancer (BC) constitutes a major health problem worldwide, making it the most common malignancy in women. Current treatment options for BC depend primarily on histological type, molecular markers, clinical aggressiveness and stage of disease. Immunotherapy, such as anti-PD-1, have shown combinatorial clinical activity with chemotherapy in triple negative breast cancer (TNBC) delineating some therapeutic combinations as more effective than others. However, a clear overview of the main immune cell populations involved in these treatments has never been provided.

Here, an assessment of the immune landscape in the tumour microenvironment (TME) of two TNBC mouse models (4T1 and EMT6 cell lines) has been performed using single-cell RNA sequencing (scRNA-seq) technology. Specifically, immune cells were evaluated in untreated conditions and after being treated with chemotherapy or immunotherapy used as single agents or in combination. A decrease of regulatory T cells, compared to the untreated TME, was found in treatments with in vivo efficacy as well as γδ T cells, which have a pro-tumoral activity in mice. Focusing on Cd8 T cells, across all the conditions, a general increase of exhausted-like Cd8 T cells was confirmed in pre-clinical treatments with low efficacy; on the other hand, an opposite trend was found for the proliferative Cd8 T cells. Regarding macrophages, M2-like cells were found enriched in treatments with low efficacy while opposite behaviour was associated with M1-like macrophages. For both cell lines, similar proportions of B cells were detected with an increase of proliferative B cells in treatments that involved cisplatin in combination with anti-PD-1. The fine-scale characterization of the immune TME in this work can lead to new insights on the diagnosis and treatment of TNBC for a possible application at the clinical level.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵5 These authors jointly supervised

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Posted December 02, 2021.
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A single-cell transcriptomic landscape of innate and adaptive intratumoral immunity in triple negative breast cancer during chemo- and immunotherapies
Laura Carpen, Paolo Falvo, Stefania Orecchioni, Giulia Mitola, Roman Hillje, Saveria Mazzara, Patrizia Mancuso, Stefano Pileri, Alessandro Raveane, Francesco Bertolini
bioRxiv 2021.12.01.470716; doi: https://doi.org/10.1101/2021.12.01.470716
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A single-cell transcriptomic landscape of innate and adaptive intratumoral immunity in triple negative breast cancer during chemo- and immunotherapies
Laura Carpen, Paolo Falvo, Stefania Orecchioni, Giulia Mitola, Roman Hillje, Saveria Mazzara, Patrizia Mancuso, Stefano Pileri, Alessandro Raveane, Francesco Bertolini
bioRxiv 2021.12.01.470716; doi: https://doi.org/10.1101/2021.12.01.470716

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