Single-cell dissection of multifocal bladder cancer reveals malignant and immune cells variation between primary and recurrent tumor lesions

Communications Biology, 2024 · DOI: https://doi.org/10.1038/s42003-024-07343-7 · Published: December 2, 2024

Simple Explanation

This study used single-cell RNA sequencing to analyze tumor lesions from five patients with multifocal bladder cancer, including both primary and recurrent tumors. The research found that malignant cells from recurrent tumors show more similarity between different regions and communicate in a consistent manner. The study also identified that recurrent tumors may evade immune destruction by suppressing cytokine responses and natural killer cell activity, with a specific enzyme, IL4I1, playing a role in this process.

Study Duration

Not specified

Participants

Five multifocal bladder cancer patients comprising three primary tumors and two recurrent tumors

Evidence Level

Level 3: Single-cell RNA sequencing analysis

Key Findings

1
Malignant cells from recurrent multifocal bladder cancer exhibited higher interregional transcriptional similarity and consistent cellular communication.
2
Malignant cells from recurrent tumors may evade immune destruction by suppressing cytokine responses and natural killer cell activity.
3
IL4I1 promotes tumor progression in recurrent tumors by activating the aryl hydrocarbon receptor (AHR) and recruiting regulatory T cells to suppress adaptive immunity.

Research Summary

The study provides a single-cell level atlas characterizing the tumor microenvironment (TME) in primary and recurrent multifocal bladder cancer (BLCA). Analyses reveal significant differences in malignant cells, immune cells, and the stromal context between recurrent and primary tumors, offering potential novel targeting strategies. Recurrent tumors exhibit a smaller degree of interregional heterogeneity compared to intertumoral heterogeneity, with malignant cells showing higher interregional similarities and more consistent communication networks.

Practical Implications

Therapeutic Targets

CD74 could serve as a promising therapeutic target for combined therapy in the treatment of recurrent bladder tumors.

Pharmacological Targets

The critical role of tryptophan metabolism in cancer therapy suggests the development of novel pharmacological targets for BLCA.

Personalized Treatment

Understanding the distinctive features observed in recurrent tumors offers opportunities for personalized treatment strategies targeting the co-evolution between malignant cells and the TME.

Study Limitations

1
Relatively small sample size resulting from sampling limitations
2
Study focused on non-muscle invasive bladder cancer (NMIBC)
3
The impact of MHC II expression on patient survival and response to immunotherapy remains controversial

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