Dynamic Immune Responsiveness in Breast Cancer: Tumor Microenvironment Plasticity, Therapeutic Timing, and Clinical Translation
- 1Department of Radiation Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9187, USA
- 2Department of Biological Sciences, University of Texas at Dallas, Richardson, TX 75080-3021, USA
Abstract
Breast cancer immunotherapy has advanced substantially, yet durable clinical benefit remains limited to selected patient populations, reflecting heterogeneity in tumor–immune interactions across molecular subtypes, disease stages, and treatment contexts. This review frames immune responsiveness as a dynamic manifestation of tumor microenvironmental plasticity rather than a fixed tumor phenotype. We integrate mechanistic evidence showing that anti-tumor immunity is governed by interactions among malignant cells, immune populations, and cancer-associated fibroblasts. We emphasize therapeutic timing where treatment-induced changes in antigen availability, immune priming, stromal architecture, and cellular composition may create transient windows of immune susceptibility. Mechanisms of immune escape, including defective antigen presentation, T-cell dysfunction, suppressive myeloid populations, stromal exclusion, vascular abnormalities, and metabolic constraints, are evaluated as potential therapeutic targets. Emerging approaches incorporating single-cell and spatial profiling, circulating tumor DNA, multiomics, digital pathology, and artificial intelligence offer approaches for longitudinal characterization of evolving immune states, but their clinical utility in guiding immunotherapy remains largely unvalidated. We propose a precision-immunotherapy framework in which treatment selection and sequencing could be informed by these states. This framework complements established treatment approaches and defines testable hypotheses for prospective clinical studies.
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BibTeX
@article{udden2026dynamic,
title = {{Dynamic Immune Responsiveness in Breast Cancer: Tumor Microenvironment Plasticity, Therapeutic Timing, and Clinical Translation}},
author = {S. M. Nashir Udden and Monira Obaid and Laurentiu M. Pop and Raquibul Hannan},
journal = {International journal of molecular sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198854},
url = {https://europepmc.org/article/PMC/PMC13665398},
note = {CC BY},
}
RIS
TY - JOUR
TI - Dynamic Immune Responsiveness in Breast Cancer: Tumor Microenvironment Plasticity, Therapeutic Timing, and Clinical Translation
AU - S. M. Nashir Udden
AU - Monira Obaid
AU - Laurentiu M. Pop
AU - Raquibul Hannan
PY - 2026
DA - 2026/10/01
JO - International journal of molecular sciences
DO - 10.3390/ijms27198854
UR - https://europepmc.org/article/PMC/PMC13665398
AB - Breast cancer immunotherapy has advanced substantially, yet durable clinical benefit remains limited to selected patient populations, reflecting heterogeneity in tumor–immune interactions across molecular subtypes, disease stages, and treatment contexts. This review frames immune responsiveness as a dynamic manifestation of tumor microenvironmental plasticity rather than a fixed tumor phenotype. We integrate mechanistic evidence showing that anti-tumor immunity is governed by interactions among malignant cells, immune populations, and cancer-associated fibroblasts. We emphasize therapeutic timing where treatment-induced changes in antigen availability, immune priming, stromal architecture, and cellular composition may create transient windows of immune susceptibility. Mechanisms of immune escape, including defective antigen presentation, T-cell dysfunction, suppressive myeloid populations, stromal exclusion, vascular abnormalities, and metabolic constraints, are evaluated as potential therapeutic targets. Emerging approaches incorporating single-cell and spatial profiling, circulating tumor DNA, multiomics, digital pathology, and artificial intelligence offer approaches for longitudinal characterization of evolving immune states, but their clinical utility in guiding immunotherapy remains largely unvalidated. We propose a precision-immunotherapy framework in which treatment selection and sequencing could be informed by these states. This framework complements established treatment approaches and defines testable hypotheses for prospective clinical studies.
SN - 1422-0067
ER -