An immunological mechanism of resistance to CDK4/6 inhibitors in HR+ breast cancer

Claudia Galassi; Giulia Petroni; Simon R.V. Knott; Lorenzo Galluzzi

doi:10.1080/2162402X.2025.2520269

An immunological mechanism of resistance to CDK4/6 inhibitors in HR⁺ breast cancer

Claudia Galassi, Giulia Petroni, Simon R.V. Knott, Lorenzo Galluzzi

Cancer Signaling and Microenvironment (CSM)

Research output: Contribution to journal › Editorial

Abstract

CDK4/6 inhibitors are central to the clinical management of HR⁺HER2⁻ breast cancer. We have recently demonstrated that immunosuppressive, IL17-secreting γδ T cells recruited to the tumor microenvironment by a CCL2-dependent mechanism upon CDK4/6 inhibition can repolarize tumor-associated macrophages toward a CX3CR1⁺ phenotype associated with resistance to therapy.

Original language	English
Article number	2520269
Journal	Oncoimmunology
Volume	14
Issue number	1
DOIs	https://doi.org/10.1080/2162402X.2025.2520269
State	Published - 2025

Keywords

Animals
Breast Neoplasms/immunology
Cyclin-Dependent Kinase 4/antagonists & inhibitors
Cyclin-Dependent Kinase 6/antagonists & inhibitors
Drug Resistance, Neoplasm/immunology
Female
Humans
Intraepithelial Lymphocytes/immunology
Protein Kinase Inhibitors/therapeutic use
Receptor, ErbB-2/metabolism
Receptors, Estrogen/metabolism
Tumor Microenvironment/immunology
Tumor-Associated Macrophages/immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1080/2162402X.2025.2520269

Cite this

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title = "An immunological mechanism of resistance to CDK4/6 inhibitors in HR+ breast cancer",

abstract = "CDK4/6 inhibitors are central to the clinical management of HR+HER2− breast cancer. We have recently demonstrated that immunosuppressive, IL17-secreting γδ T cells recruited to the tumor microenvironment by a CCL2-dependent mechanism upon CDK4/6 inhibition can repolarize tumor-associated macrophages toward a CX3CR1+ phenotype associated with resistance to therapy.",

keywords = "Animals, Breast Neoplasms/immunology, Cyclin-Dependent Kinase 4/antagonists \& inhibitors, Cyclin-Dependent Kinase 6/antagonists \& inhibitors, Drug Resistance, Neoplasm/immunology, Female, Humans, Intraepithelial Lymphocytes/immunology, Protein Kinase Inhibitors/therapeutic use, Receptor, ErbB-2/metabolism, Receptors, Estrogen/metabolism, Tumor Microenvironment/immunology, Tumor-Associated Macrophages/immunology",

author = "Claudia Galassi and Giulia Petroni and Knott, \{Simon R.V.\} and Lorenzo Galluzzi",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Published with license by Taylor \& Francis Group, LLC.",

year = "2025",

doi = "10.1080/2162402X.2025.2520269",

language = "English",

volume = "14",

journal = "Oncoimmunology",

issn = "2162-4011",

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TY - JOUR

T1 - An immunological mechanism of resistance to CDK4/6 inhibitors in HR+ breast cancer

AU - Galassi, Claudia

AU - Petroni, Giulia

AU - Knott, Simon R.V.

AU - Galluzzi, Lorenzo

PY - 2025

Y1 - 2025

N2 - CDK4/6 inhibitors are central to the clinical management of HR+HER2− breast cancer. We have recently demonstrated that immunosuppressive, IL17-secreting γδ T cells recruited to the tumor microenvironment by a CCL2-dependent mechanism upon CDK4/6 inhibition can repolarize tumor-associated macrophages toward a CX3CR1+ phenotype associated with resistance to therapy.

AB - CDK4/6 inhibitors are central to the clinical management of HR+HER2− breast cancer. We have recently demonstrated that immunosuppressive, IL17-secreting γδ T cells recruited to the tumor microenvironment by a CCL2-dependent mechanism upon CDK4/6 inhibition can repolarize tumor-associated macrophages toward a CX3CR1+ phenotype associated with resistance to therapy.

KW - Animals

KW - Breast Neoplasms/immunology

KW - Cyclin-Dependent Kinase 4/antagonists & inhibitors

KW - Cyclin-Dependent Kinase 6/antagonists & inhibitors

KW - Drug Resistance, Neoplasm/immunology

KW - Female

KW - Humans

KW - Intraepithelial Lymphocytes/immunology

KW - Protein Kinase Inhibitors/therapeutic use

KW - Receptor, ErbB-2/metabolism

KW - Receptors, Estrogen/metabolism

KW - Tumor Microenvironment/immunology

KW - Tumor-Associated Macrophages/immunology

UR - https://www.scopus.com/pages/publications/105010580902

U2 - 10.1080/2162402X.2025.2520269

DO - 10.1080/2162402X.2025.2520269

M3 - Editorial

C2 - 40662849

AN - SCOPUS:105010580902

SN - 2162-4011

VL - 14

JO - Oncoimmunology

JF - Oncoimmunology

IS - 1

M1 - 2520269

ER -