MINI REVIEW article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1617906

This article is part of the Research TopicCommunity Series in Interaction of Cell Subtypes in Tumor Microenvironment, and Implications for Immunotherapy Volume IIView all articles

Multiplex imaging analysis of the tumor immune microenvironment for guiding precision immunotherapy

Provisionally accepted
Kang  LiuKang Liu*Feng  LiuFeng LiuGuiqing  LiGuiqing LiYi  ZhengYi Zheng
  • Shandong Second Medical University, Weifang, China

The final, formatted version of the article will be published soon.

Cutting-edge mMultiplex imaging technologies have significantly advanced our understanding of the tumor immune microenvironment (TIME), delivering nanometer-scaleoffering unprecedented spatial resolution that illuminates previously inaccessible cellular interactions and organizational patternsof cellular interactions. This mini-review discusses the latest multiplex imaging methods, including Imaging Mass Cytometry (IMC), Multiplexed Ion Beam Imaging (MIBI), Cyclic Immunofluorescence (CycIF), and Digital Spatial Profiling (DSP), emphasizing their roles in identifying spatial immune signatures predictive of immunotherapy responses. Clinical applications across various cancers-such as NSCLC, melanoma, breast cancer, colorectal cancer, and hepatocellular carcinoma-highlight how spatially resolved immune profiles can enhance patient stratification and treatment personalization. For instance, in NSCLC, increased CD8⁺ T cell density in tumor cores has been associated with objective response rates exceeding 45% to PD-1 blockade combined with chemotherapy, while in melanoma, spatial colocalization of CD8⁺ T cells and tumor cells correlates with improved survivalNotably, increased CD8⁺ T cell density and spatial colocalization with tumor cells have been broadly correlated with improved immunotherapy response and survival across multiple cancer types. Despite current technical and analytical challenges, ongoing technological advancements and integration with emerging methods like spatial transcriptomics and super-resolution imaging promise broader clinical utility, ultimately improving patient outcomes in precision immunotherapy.

Keywords: tumor immune microenvironment (TIME), Multiplex imaging, Spatial profiling, Immune Cell Interactions, immunotherapy biomarkers

Received: 25 Apr 2025; Accepted: 24 Jun 2025.

Copyright: © 2025 Liu, Liu, Li and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Kang Liu, Shandong Second Medical University, Weifang, China

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