Innate immune cells in tumor immunity: dual roles, mechanistic insights, and therapeutic opportunities
- 1Cancer Center, The First Hospital of Jilin University, Jilin University
- 2Department of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, Jilin University
- 3School of Life Sciences, Jilin University
Abstract
The tumor microenvironment (TME) is a complex ecosystem that dynamically regulates tumor progression and therapeutic responses. Within this environment, innate immune cells play prominent dual roles, acting as both critical mediators of anti-tumor surveillance and facilitators of tumor immune escape. This review comprehensively synthesizes the phenotypic plasticity and functional heterogeneity of key innate immune cell subsets in tumor immunity, including tumor-associated macrophages (TAMs), natural killer (NK) cells, tumor-associated neutrophils (TANs), dendritic cells (DCs), as well as emerging players such as γδ T cells and innate lymphoid cells (ILCs). Mechanistically, we dissect core pathways governing innate immune cell function in the TME: the cGAS-STING pathway regulates type I interferon responses and immunogenicity; the NF-κB/STAT3 network coordinates inflammation and immunosuppression; the PD-1/PD-L1 axis mediates T cell exhaustion and innate cell dysfunction. Additionally, tumor-driven metabolic reprogramming and extracellular vesicles (EVs) intercellular communication collectively shape the immunosuppressive TME. We further evaluate emerging therapeutic strategies targeting innate immunity. This narrative review provides a comprehensive mechanistic framework and theoretical basis for developing precise, innate immunity-targeted cancer immunotherapies.
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BibTeX
@article{xing2026innate,
title = {{Innate immune cells in tumor immunity: dual roles, mechanistic insights, and therapeutic opportunities}},
author = {Songhang Xing and Jiayu Zhang and Shuang Wang and Yuan Hao and Dan Huang and Manwei Hao and Wurihan Bao and Xiaojie Qu and Yanyan Chi and Xuefeng Li},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1923822},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1923822/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Innate immune cells in tumor immunity: dual roles, mechanistic insights, and therapeutic opportunities
AU - Songhang Xing
AU - Jiayu Zhang
AU - Shuang Wang
AU - Yuan Hao
AU - Dan Huang
AU - Manwei Hao
AU - Wurihan Bao
AU - Xiaojie Qu
AU - Yanyan Chi
AU - Xuefeng Li
PY - 2026
DA - 2026/10/05
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1923822
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1923822/full
AB - The tumor microenvironment (TME) is a complex ecosystem that dynamically regulates tumor progression and therapeutic responses. Within this environment, innate immune cells play prominent dual roles, acting as both critical mediators of anti-tumor surveillance and facilitators of tumor immune escape. This review comprehensively synthesizes the phenotypic plasticity and functional heterogeneity of key innate immune cell subsets in tumor immunity, including tumor-associated macrophages (TAMs), natural killer (NK) cells, tumor-associated neutrophils (TANs), dendritic cells (DCs), as well as emerging players such as γδ T cells and innate lymphoid cells (ILCs). Mechanistically, we dissect core pathways governing innate immune cell function in the TME: the cGAS-STING pathway regulates type I interferon responses and immunogenicity; the NF-κB/STAT3 network coordinates inflammation and immunosuppression; the PD-1/PD-L1 axis mediates T cell exhaustion and innate cell dysfunction. Additionally, tumor-driven metabolic reprogramming and extracellular vesicles (EVs) intercellular communication collectively shape the immunosuppressive TME. We further evaluate emerging therapeutic strategies targeting innate immunity. This narrative review provides a comprehensive mechanistic framework and theoretical basis for developing precise, innate immunity-targeted cancer immunotherapies.
SN - 1664-3224
ER -