Unlabelled: Immune-regulated pathways influence multiple aspects of cancer development. In this article we demonstrate that both macrophage abundance and T-cell abundance in breast cancer represent prognostic indicators for recurrence-free and overall survival. We provide evidence that response to chemotherapy is in part regulated by these leukocytes; cytotoxic therapies induce mammary epithelial cells to produce monocyte/macrophage recruitment factors, including colony stimulating factor 1 (CSF1) and interleukin-34, which together enhance CSF1 receptor (CSF1R)-dependent macrophage infiltration. Blockade of macrophage recruitment with CSF1R-signaling antagonists, in combination with paclitaxel, improved survival of mammary tumor-bearing mice by slowing primary tumor development and reducing pulmonary metastasis. These improved aspects of mammary carcinogenesis were accompanied by decreased vessel density and appearance of antitumor immune programs fostering tumor suppression in a CD8+ T-cell-dependent manner. These data provide a rationale for targeting macrophage recruitment/response pathways, notably CSF1R, in combination with cytotoxic therapy, and identification of a breast cancer population likely to benefit from this novel therapeutic approach.

Significance: These findings reveal that response to chemotherapy is in part regulated by the tumor immune microenvironment and that common cytotoxic drugs induce neoplastic cells to produce monocyte/macrophage recruitment factors, which in turn enhance macrophage infiltration into mammary adenocarcinomas. Blockade of pathways mediating macrophage recruitment, in combination with chemotherapy, significantly decreases primary tumor progression, reduces metastasis, and improves survival by CD8+ T-cell-dependent mechanisms, thus indicating that the immune microenvironment of tumors can be reprogrammed to instead foster antitumor immunity and improve response to cytotoxic therapy.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203524PMC
http://dx.doi.org/10.1158/2159-8274.CD-10-0028DOI Listing

Publication Analysis

Top Keywords

breast cancer
12
response chemotherapy
12
chemotherapy regulated
8
cells produce
8
produce monocyte/macrophage
8
monocyte/macrophage recruitment
8
recruitment factors
8
macrophage infiltration
8
macrophage recruitment
8
primary tumor
8

Similar Publications

Unveiling the role of PANoptosis-related genes in breast cancer: an integrated study by multi-omics analysis and machine learning algorithms.

Breast Cancer Res Treat

January 2025

Department of Breast Surgery, Thyroid Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, No.141, Tianjin Road, Huangshi, 435000, Hubei, China.

Background: The heterogeneity of breast cancer (BC) necessitates the identification of novel subtypes and prognostic models to enhance patient stratification and treatment strategies. This study aims to identify novel BC subtypes based on PANoptosis-related genes (PRGs) and construct a robust prognostic model to guide individualized treatment strategies.

Methods: The transcriptome data along with clinical data of BC patients were sourced from the TCGA and GEO databases.

View Article and Find Full Text PDF

Purpose: Aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) are the most common adverse effects experienced by breast cancer patients. This scoping review aimed to systematically synthesize the predictors/risk factors and outcomes of AIMSS in patients with early-stage breast cancer.

Methods: A systematic search was conducted in PubMed, Web of Science, EMBASE, CINAHL, and the China National Knowledge Internet (CNKI) from inception to December 2024 following the scoping review framework proposed by Arksey and O'Malley (2005).

View Article and Find Full Text PDF

Prognosis of Implant-Based Breast Reconstruction After Mastectomy Flap Necrosis: Predictors of Failure and Salvage.

Aesthetic Plast Surg

January 2025

Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

Background: In the realm of implant-based breast reconstruction, mastectomy flap necrosis (MFN) is a prevalent yet grave complication that poses a threat to the stability of the inserted prosthesis. Although numerous investigations have scrutinized the risk factors for MFN development, few have delved into the aftermath, specifically implant failure or salvage. This study seeks to appraise the prognosis of the implanted prosthesis following MFN occurrence, as well as identify predictors of such outcomes.

View Article and Find Full Text PDF

The role of human epidermal growth factor 2 (HER2) in male breast cancer (MBC) is poorly defined. A comprehensive description of HER2 status was conducted. A total of 6,015 MBC patients from 45 studies and 135 MBC patients with sequencing data were identified.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!