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CD103+CD8+ tissue-resident memory T cell infiltration predicts clinical outcome and adjuvant therapeutic benefit in muscle-invasive bladder cancer

British Journal of Cancer volume 126, pages 1581–1588 (2022)Cite this article

Subjects

Abstract

Background

CD103+CD8+ tissue-resident memory T (TRM) cells, associated with better overall survival among various malignancies, are thought to activate anti-tumour immune response and affect therapeutic sensitivity including both immunotherapy and adjuvant chemotherapy (ACT).

Methods

Totally 650 muscle-invasive bladder cancer (MIBC) patients from three independent cohorts were included in this study for survival and cisplatin-based ACT response analysis. Another public data set consisting of 195 patients from IMvigor210 trial receiving PD-L1 blockade were involved in the assessment of immunotherapeutic response. Fifty-nine fresh tumour tissues were used to evaluate immune infiltration of CD103+CD8+ TRM cells.

Results

Patients with high CD103+CD8+ TRM cells infiltration, but not CD8+ T cells, are more likely to benefit from immunotherapy and ACT. The presence of TRM cells is highly associated with an enhanced IFNγ-enriched and T cell-inflamed anti-tumour microenvironment. Elevated CD103+CD8+ TRM cells infiltration correlated with superior ACT response in mismatch repair (MMR), homologous recombination (HR), PIK3CA/AKT and RAS/RAF pathway proficient or histone modification and cell cycle pathway deficient patients.

Conclusions

CD103+CD8+ TRM cells played a crucial role in anti-tumour immunity and served as an ideal prognostic biomarker. It could be treated as a superior companion predictor for treatment response to PD-L1 inhibitor and ACT within MIBC patients.

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Fig. 1: Flow chart of cohort selection.
Fig. 2: CD103+CD8+ TRM cells correlated with better therapeutic response to PD-L1 blockade in IMvigor210 trial.
Fig. 3: CD103+CD8+ TRM cells predict better overall survival and superior response to adjuvant chemotherapy in patients with MIBC.
Fig. 4: CD103+CD8+ TRM cells shape an anti-tumour immune microenvironment.
Fig. 5: Characterisation of CD8+ T and CD103+CD8+ TRM cells infiltration across molecular features and prognostic value under prime mutations.

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Data availability

All data relevant to the study are included in the article or uploaded as Supplementary Information. Other data are available upon reasonable request.

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Acknowledgements

We thank Dr. Lingli Chen (Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China) and Dr. Yunyi Kong (Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China) for their excellent pathological technology help.

Funding

This study was funded by grants from the National Natural Science Foundation of China (31770851, 81872082, 82002670, 82103408), Shanghai Municipal Natural Science Foundation (19ZR1431800), Shanghai Sailing Program (18YF1404500, 21YF1407000), Shanghai Municipal Commission of Health and Family Planning Program (201840168) and Fudan University Shanghai Cancer Center for Outstanding Youth Scholars Foundation (YJYQ201802). All these study sponsors have no roles in the study design, in the collection, analysis and interpretation of data.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Kaifeng Jin, Yanze Yu, Han Zeng, Zhaopei Liu, Runze You, Hongyi Zhang, Chunnan Liu, Xiaohe Su, Sen Yan & Jiejie Xu

  2. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China

    Yuan Chang & Yu Zhu

  3. Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Le Xu

  4. Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China

    Zewei Wang

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  1. Kaifeng Jin
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Contributions

KJ: acquisition of data, analysis and interpretation of data, statistical analysis and drafting of the manuscript; YY, H Zeng, ZL, RY, H Zhang, CL, XS, SY, YC and LX: technical and material support; JX, YZ and ZW: study concept and design, analysis and interpretation of data, drafting of the manuscript, obtained funding and study supervision. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jiejie Xu, Yu Zhu or Zewei Wang.

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The authors declare no competing interests.

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This study was approved by the Clinical Research Ethics Committee of Zhongshan Hospital, Fudan University (No. B2015-030) and the Ethics Committee of Fudan University Shanghai Cancer Center (No. 050432-4-1212B). Written informed consent was obtained from each patient.

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Jin, K., Yu, Y., Zeng, H. et al. CD103+CD8+ tissue-resident memory T cell infiltration predicts clinical outcome and adjuvant therapeutic benefit in muscle-invasive bladder cancer. Br J Cancer 126, 1581–1588 (2022). https://doi.org/10.1038/s41416-022-01725-6

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