Organoid and organ-on-a-chip models for the tumor immune microenvironment: Integrating immunosenescence into next-generation platforms

Yining Feng; Luqi Wang; Dameng Li; Chenglong Mu; Liang Wei; Bo Ma

doi:10.70401/acrt.2026.0039

Organoid and organ-on-a-chip models for the tumor immune microenvironment: Integrating immunosenescence into next-generation platforms

Yining Feng

1,#

Luqi Wang

1,#

Dameng Li

1,2,3,#

Chenglong Mu

1,2,3,#

Liang Wei

1,2,3,*

Bo Ma

1,2,3,*

Affiliation +

*Correspondence to: Bo Ma, Cellular Therapeutics School of Medicine, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China. E-mail: boma@xzhmu.edu.cn
Liang Wei, Cellular Therapeutics School of Medicine, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China. E-mail: weiliang@xzhmu.edu.cn

Ageing Cancer Res Treat. 2026;3:202625. 10.70401/acrt.2026.0039

Received: May 26, 2026Accepted: September 02, 2026Published: September 03, 2026

This article belongs to the Special lssue Immunosenescence and Cancer: From Mechanisms to Therapy

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

The tumor immune microenvironment (TIME) is a central determinant of cancer progression and therapeutic response. Although organoid and organ-on-a-chip technologies have substantially advanced the modeling of tumor-immune interactions, most current platforms overlook a critical dimension of clinical reality, immunosenescence. This process profoundly reshapes immune cell composition, functional capacity, and tumor-immune crosstalk, yet remains largely absent from existing in vitro systems. In this review, we provide a conceptual and methodological overview of organoid- and microfluidic-based models for reconstructing the TIME. We highlight their respective strengths in capturing tumor heterogeneity and dynamic immune processes, while critically evaluating their limitations in modeling long-term immune evolution and age-associated dysfunction. Importantly, we propose immunosenescence as a missing but essential modeling axis and argue that it should be treated as a controllable experimental variable rather than a background condition. By integrating aging-associated immune features into advanced 3D and microfluidic platforms, next-generation models are poised to better recapitulate patient heterogeneity and improve the prediction of immunotherapy outcomes. This perspective underscores a shift toward age-aware, physiologically relevant tumor models and provides a framework for advancing precision immuno-oncology in an aging population.

Keywords

Tumor immune microenvironment, immunosenescence, organoid, organ-on-a-chip

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Feng Y, Wang L, Li D, Mu C, Wei L, Ma B. Organoid and organ-on-a-chip models for the tumor immune microenvironment: Integrating immunosenescence into next-generation platforms. Ageing Cancer Res Treat. 2026;3:202625. https://doi.org/10.70401/acrt.2026.0039