The New Frontier of Immunotherapy - Chimeric Antigen Receptor T (CAR-T) Cell and Macrophage (CAR-M) Therapy against Breast Cancer

Sep 24, 2026

Uploaded by Jiven

Breast cancer is among the most common tumor histologies, and survival benefits have been achieved through immunotherapy-based strategies tailored to specific histotypes. Results from CAR-T cell therapy in hematological malignancies have driven translation of chimeric antigen receptor approaches to solid tumors. This article focuses on CAR-T cell and CAR-M macrophage therapy in breast cancer, linking immunobiology to emerging therapeutic directions. It highlights how receptor-defined patient subtypes motivate novel CAR-based immunotherapeutic research.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Review

Title and citation information

Simple Summary

Abstract

Keywords

1. Introduction

Breast cancer subtypes and unmet need

Immunotherapy rationale in TNBC

Tumor mutational burden and neoantigens

Tumor microenvironment and immune infiltration

cancers Review The New Frontier of Immunotherapy: Chimeric Antigen Receptor T (CAR-T) Cell and Macrophage (CAR-M) Therapy against Breast Cancer Giuseppe Schepisi *, Caterina Gianni , Michela Palleschi , Sara Bleve, Chiara Casadei , Cristian Lolli, Laura Ridolﬁ , Giovanni Martinelli and Ugo De Giorgi Citation: Schepisi, G.; Gianni, C.; Palleschi, M.; Bleve, S.; Casadei, C.; Lolli, C.; Ridolﬁ, L.; Martinelli, G.; De Giorgi, U. The New Frontier of Immunotherapy: Chimeric Antigen Receptor T (CAR-T) Cell and Macrophage (CAR-M) Therapy against Breast Cancer. Cancers 2023, 15, 1597. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cancers15051597 Academic Editor: Simone Krebs Received: 27 December 2022 Revised: 1 March 2023 Accepted: 3 March 2023 Published: 4 March 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST)“Dino Amadori”, 47014 Meldola, Italy * Correspondence: [giuseppe.schepisi@irst.emr.it](giuseppe.schepisi@irst.emr.it) Simple Summary: To date, different therapeutic strategies, including immunotherapies, have been shown to prolong survival in breast cancer patients, representing one of the most common malignancies. Our article deals with chimeric antigen receptor-based immunotherapy in breast cancer. Abstract: Breast cancer represents one of the most common tumor histologies. To date, based on the speciﬁc histotype, different therapeutic strategies, including immunotherapies, capable of prolonging survival are used. More recently, the astonishing results that were obtained from CAR-T cell therapy in haematological neoplasms led to the application of this new therapeutic strategy in solid tumors as well. Our article will deal with chimeric antigen receptor-based immunotherapy (CAR-T cell and CAR-M therapy) in breast cancer. Keywords: chimeric antigen receptor (CAR); macrophages; T cells; immunotherapy; breast cancer 1. Introduction Breast cancer (BC) is the most common female cancer worldwide. According to Globocan, it is the number one diagnosed cancer with an estimated 2.3 million new cases (11.7%) globally in 2020, and is the ﬁfth leading cause of cancer mortality [1] . The BC incidence is increasing, especially in highly developed countries where screening strategies help to reduce cancer mortality while in poor-developing countries, the BC incidence remains low but the mortality rate is still higher [1] . However, in advanced countries, the diagnosis of de novo metastatic BC still represents approximately 3% to 6% of new BC diagnoses and has not declined despite the wide diffusion of mammography screening [2] . BC is a very heterogeneous disease, clinically distinguished into several subtypes according to the expression of hormone receptors (HRs) and the human epidermal growth factor receptor 2 (HER-2) status: luminal BC, HER-2 positive BC, and triple-negative BC (TNBC) . HR and HER-2 are the targets for numerous speciﬁc treatments in early and advanced settings. TNBC is deﬁned by the lack of expression of HR and HER-2 and accounts for approximately 15% of all BCs [3] . TNBC has long been considered a major unmet need due to its aggressive behavior and poor prognosis related to its deﬁciency of speciﬁc therapeutic targets. These tumors tend to relapse early and rapidly metastasize in the lungs, liver, and central nervous system, determining a worse survival [4] . For these reasons, chemotherapy is still a cornerstone in the treatment of this BC subtype. Immunotherapy with checkpoint inhibitors was shown to be effective in TNBC, especially in the case of programmed death 1 (PD-1) expre

FAQs

What therapeutic strategies does the article discuss for breast cancer?

The article discusses immunotherapy-based strategies, with a focus on chimeric antigen receptor approaches. It specifically addresses CAR-T cell therapy and CAR-M macrophage therapy in breast cancer.

Why is triple-negative breast cancer (TNBC) described as an unmet need?

TNBC is characterized by aggressive behavior and poor prognosis due to limited targeted therapies. It tends to relapse early, metastasize rapidly, and leads to worse survival.

How do tumor mutational burden and neoantigens relate to immunotherapy in TNBC?

TNBC has the highest tumor mutational burden among breast cancer subtypes, which can generate neoantigens. These neoantigens may be recognized by antigen-presenting cells in the tumor microenvironment, enhancing antitumor immune responses.

Sep 24, 2026

Uploaded by Jiven