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Immune microenvironment in different molecular subtypes of ductal breast carcinoma

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Abstract

Purpose

Ductal breast carcinoma as a heterogeneous disease has different molecular subtypes associated with clinical prognosis and patients’ survival. The role of immune system as a consistent part of the tumor microenvironment (TME) has been documented in progression of ductal breast carcinoma. Here, we aimed to describe the important immune cells and the immune system-associated molecules in Ductal Carcinoma In situ (DCIS) and Invasive Ductal Carcinoma (IDC) with special emphasis on their associations with different molecular subtypes and patients’ prognosis.

Results

The immune cells have a dual role in breast cancer (BC) microenvironment depending on the molecular subtype or tumor grade. These cells with different frequencies are present in the TME of DCIS and IDC. The presence of regulatory cells including Tregs, MDSC, Th2, Th17, M2 macrophages, HLADR− T cells, and Tγδ cells is related to more immunosuppressive microenvironment, especially in ER− and TN subtypes. In contrast, NK cells, CTL, Th, and Tfh cells are associated to the anti-tumor activity. These cells are higher in ER+ BC, although in other subtypes such as TN or HER2+ are associated with a favorable prognosis.

Conclusion

Determining the specific immune response in each subtype could be helpful in estimating the possible behavior of the tumor cells in TME. It is important to realize that different frequencies of immune cells in BC environment likely determine the patients’ prognosis and their survival in each subtype. Therefore, elucidation of the distinct immune players in TME would be helpful toward developing targeted therapies in each subtype.

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Abbreviations

BC:

Breast cancer

CTL:

Cytotoxic T lymphocyte

CTLA-4:

Cytotoxic T lymphocyte antigen 4

DCIS:

Ductal carcinoma in situ

DFS:

Disease-free survival

ELF5:

E74-like factor 5

EMT:

Epithelial–mesenchymal transition

ER:

Estrogen receptor

HER2:

Human epidermal growth factor receptor 2

iCTLA-4:

Intracellular CTLA-4

IDC:

Invasive ductal carcinoma

ILC:

Innate lymphoid cell

LAG-3:

Lymphocyte-activation gene-3

MDSC:

Myeloid-derived suppressor cell

NCT:

Neoadjuvant chemotherapy

NET:

Neutrophil extracellular trap

NK:

Natural killer cells

NLR:

Neutrophil to lymphocyte ratio

OS:

Overall survival

pCR:

Pathologic complete response

PD-1:

Programmed cell death protein-1

PD-L1:

Programmed death ligand-1

PLR:

Platelet to lymphocyte ratio

PR:

Progesterone receptor

TAM:

Tumor-associated macrophage

TAN:

Tumor-associated neutrophil

Tfh:

Follicular T helper cell

Th1:

Type 1 helper T cells

Th2:

Type 2 helper T-cell

TIL:

Tumor-infiltrating lymphocyte

TIM-3:

T-cell immunoglobulin and mucin domain

TLS:

Tertiary lymphoid structure

TME:

Tumor microenvironment

TN:

Triple-negative

TNBC:

Triple-negative breast cancer

Treg:

Regulatory T-cell

Tγδ:

Gamma delta T-cell

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Acknowledgements

Effective, instructive and valuable comments, provided by the respected reviewers and editor are gratefully acknowledged.

Funding

This study was supported by a grant from Tehran University of Medical Sciences (Grant Number 41086).

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Authors and Affiliations

  1. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Mona Sadeghalvad & Nima Rezaei

  2. Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Mona Sadeghalvad

  3. Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Hamid-Reza Mohammadi-Motlagh

  4. Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei

  5. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Mona Sadeghalvad & Nima Rezaei

  6. Children’s Medical Center Hospital, Dr Qarib St, Keshavarz Blvd, 14194, Tehran, Iran

    Nima Rezaei

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  1. Mona Sadeghalvad
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  2. Hamid-Reza Mohammadi-Motlagh
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Correspondence to Nima Rezaei.

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MS declares that she has no conflict of interest. HM declares that he has no conflict of interest. NR has received research grant from Tehran University of Medical Sciences (Grant Number 41086).

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Sadeghalvad, M., Mohammadi-Motlagh, HR. & Rezaei, N. Immune microenvironment in different molecular subtypes of ductal breast carcinoma. Breast Cancer Res Treat 185, 261–279 (2021). https://doi.org/10.1007/s10549-020-05954-2

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