Aniview Support Cancer Immunotherapy Research: Identification of ADAM12 as a Fibroblast Checkpoint via Single-Cell Screening

New progress has been made in identifying novel targets for cancer immunotherapy through single-cell screening.

Academician Zemin Zhang’s research team from Chongqing Medical University, in collaboration with researchers from Peking University, published a paper titled “Single-cell screens identify ADAM12 as a fibroblast checkpoint impeding anti-tumor immunity” in the journal Cancer Cell (IF = 47.2, top journal in Q1).

In this study, the researchers identified ADAM12 as a fibroblast checkpoint that impairs anti-tumor immunity. Loss of ADAM12 was shown to delay tumor progression and enhance tumor sensitivity to immunotherapy, highlighting its potential as a novel therapeutic target.

Figure 1: Experimental workflow / flow chart of the experiment.

A central challenge in tumor immunotherapy is the limited responsiveness of tumors to treatment, which is closely associated with the abundance of immunosuppressive cancer-associated fibroblasts (CAFs) within the tumor microenvironment. However, CAFs exhibit high heterogeneity and remarkable phenotypic plasticity. How to precisely reprogram CAFs from a tumor-promoting state to a tumor-suppressive state remains an unresolved issue in the field.

In this study, computational biology was integrated with high-throughput functional screening to investigate fibroblast targets. The research team first performed integrative analysis of multi-omics clinical datasets to computationally identify 54 candidate key genes. Meanwhile, a patient-derived fibroblast library was established, and CRISPRi/a Perturb-seq technology was employed for functional screening. For the first time, a genotype–phenotype causal regulatory network was systematically mapped in patient-derived CAFs. The study revealed a critical antagonistic relationship between the type I interferon response program and the myofibroblast activation program, with ADAM12 serving as a central regulatory hub of this balance. Targeting ADAM12 effectively activates the antitumor interferon response in CAFs and remodels the tumor microenvironment. Experimental results demonstrated that this strategy significantly inhibited tumor growth and enhanced CD8⁺ T cell infiltration and function across multiple mouse models. Moreover, when combined with PD-L1 blockade therapy, it exhibited synergistic therapeutic effects in resistant models.

This study establishes a comprehensive paradigm from target discovery to mechanistic validation, revealing an actionable reprogramming pathway for CAFs. It identifies ADAM12 as a novel therapeutic target characterized by minimal expression in normal tissues, along with high efficacy and potential safety. These findings provide a new strategy and promising avenue for overcoming resistance to immunotherapy, particularly for transforming “cold” tumor microenvironments.

Experiments using Aniview

Fifteen days after implantation of orthotopic Lewis lung carcinoma, mice were intraperitoneally injected with luciferin substrate. Ten minutes later, the mice were sacrisficed, and the lungs were excised for ex vivo tumor burden quantification using the AniView multimodal in vivo imaging system 

Figure 2: Orthotopic Lewis lung carcinoma 

DOI: 10.1016/j.ccell.2025.12.018