Persistent post-treatment host immune remodeling in cancer: linking therapy to minimal residual disease, relapse, and treatment rechallenge
Abstract
Anticancer therapy reshapes not only malignant cells but also immune and non-malignant host compartments. Although cancer-ecosystem, treatment-induced host-response, tumor-dormancy, and therapy-persistent residual-disease frameworks have established the importance of these interactions, they rarely distinguish transient treatment effects from immune-host alterations that persist after pharmacologic clearance and acute tissue recovery. In this Review, we use persistent post-treatment host immune remodeling to denote the immunologically consequential component of a broader persistent post-treatment host state: an exposure-linked, measurable, and potentially reversible configuration of non-malignant host compartments that persists beyond the acute treatment window and alters antitumor immune surveillance, residual-disease fate, or the response to subsequent therapy. We propose a four-phase model comprising acute host perturbation, compensatory repair, post-treatment state consolidation, and residual-disease outcome or treatment rechallenge. Persistent remodeling may arise through emergency myelopoiesis, inflammatory or immunosuppressive memory, senescence-associated secretory programs, endothelial and coagulation changes, extracellular-matrix remodeling, microbial dysbiosis, systemic metabolic decline, neuroendocrine stress, and therapy-selected clonal hematopoiesis. These processes can reshape immune surveillance and determine whether residual cancer cells are eliminated, maintained in dormancy, intermittently awakened, or driven toward sustained relapse and immune escape. We further distinguish persistent host immune remodeling from acute toxicity, baseline host susceptibility, and direct tumor-cell adaptation; separate biomarkers of residual tumor burden from biomarkers of host immune permissiveness; and outline longitudinal measurements and host-directed interventions that could inform relapse interception and treatment sequencing. Integrating residual tumor burden with the immune readiness of the treated host may provide a testable framework for minimal residual disease and rational treatment rechallenge.
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BibTeX
@article{xue2026persistent,
title = {{Persistent post-treatment host immune remodeling in cancer: linking therapy to minimal residual disease, relapse, and treatment rechallenge}},
author = {Jingnan Xue and Longhao Zhang and Cong Ning and Kai Zhang and Ziyu Xun and Zhihong Chen and Han Zheng and Chengjie Li and Mingjian Piao and Kai Zhou and Xin Lu},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1992385},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1992385},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Persistent post-treatment host immune remodeling in cancer: linking therapy to minimal residual disease, relapse, and treatment rechallenge
AU - Jingnan Xue
AU - Longhao Zhang
AU - Cong Ning
AU - Kai Zhang
AU - Ziyu Xun
AU - Zhihong Chen
AU - Han Zheng
AU - Chengjie Li
AU - Mingjian Piao
AU - Kai Zhou
AU - Xin Lu
PY - 2026
DA - 2026/11/02
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1992385
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1992385
AB - Anticancer therapy reshapes not only malignant cells but also immune and non-malignant host compartments. Although cancer-ecosystem, treatment-induced host-response, tumor-dormancy, and therapy-persistent residual-disease frameworks have established the importance of these interactions, they rarely distinguish transient treatment effects from immune-host alterations that persist after pharmacologic clearance and acute tissue recovery. In this Review, we use persistent post-treatment host immune remodeling to denote the immunologically consequential component of a broader persistent post-treatment host state: an exposure-linked, measurable, and potentially reversible configuration of non-malignant host compartments that persists beyond the acute treatment window and alters antitumor immune surveillance, residual-disease fate, or the response to subsequent therapy. We propose a four-phase model comprising acute host perturbation, compensatory repair, post-treatment state consolidation, and residual-disease outcome or treatment rechallenge. Persistent remodeling may arise through emergency myelopoiesis, inflammatory or immunosuppressive memory, senescence-associated secretory programs, endothelial and coagulation changes, extracellular-matrix remodeling, microbial dysbiosis, systemic metabolic decline, neuroendocrine stress, and therapy-selected clonal hematopoiesis. These processes can reshape immune surveillance and determine whether residual cancer cells are eliminated, maintained in dormancy, intermittently awakened, or driven toward sustained relapse and immune escape. We further distinguish persistent host immune remodeling from acute toxicity, baseline host susceptibility, and direct tumor-cell adaptation; separate biomarkers of residual tumor burden from biomarkers of host immune permissiveness; and outline longitudinal measurements and host-directed interventions that could inform relapse interception and treatment sequencing. Integrating residual tumor burden with the immune readiness of the treated host may provide a testable framework for minimal residual disease and rational treatment rechallenge.
SN - 1664-3224
ER -