Oncogenic ACSM6 impairs CD8⁺ T cell-based immune response in bladder cancer

Zhenyu Nie^#^{1

2}, Bolong Liu^#^{1

3}, Jinhui Liu^{1

2}, Xiongbing Zu^{1

4

5}, Juanhua Wang⁶, Jinbo Chen^{7

8}, Benyi Fan^{9

10}, Dingshan Deng^{11

12}

Affiliations

¹ Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
³ Department of andrology, The First Affiliated Hospital Of University Of South China, University Of South China, Hengyang, China.
⁴ Department of Urology, Hunan Provincial People's Hospital, Changsha, China.
⁵ Department of Urology, The First Affiliated Hospital of Hunan Normal University, Hunan Normal University, Changsha, China.
⁶ Hunan Vocational and Technical College of Environmental Biology, Changsha, China.
⁷ Department of Urology, Xiangya Hospital, Central South University, Changsha, China. chenjinbo@csu.edu.cn.
⁸ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. chenjinbo@csu.edu.cn.
⁹ Department of Urology, Xiangya Hospital, Central South University, Changsha, China. fanbenyi2009@yeah.net.
¹⁰ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. fanbenyi2009@yeah.net.
¹¹ Department of Urology, Xiangya Hospital, Central South University, Changsha, China. dds15116217256@163.com.
¹² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. dds15116217256@163.com.

^# Contributed equally.

PMID: 39334304
PMCID: PMC11437728
DOI: 10.1186/s40364-024-00657-y

Oncogenic ACSM6 impairs CD8⁺ T cell-based immune response in bladder cancer

Zhenyu Nie et al. Biomark Res. 2024.

. 2024 Sep 27;12(1):112.

doi: 10.1186/s40364-024-00657-y.

Authors

Zhenyu Nie^#^{1

2}, Bolong Liu^#^{1

3}, Jinhui Liu^{1

2}, Xiongbing Zu^{1

4

5}, Juanhua Wang⁶, Jinbo Chen^{7

8}, Benyi Fan^{9

10}, Dingshan Deng^{11

12}

Affiliations

¹ Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
³ Department of andrology, The First Affiliated Hospital Of University Of South China, University Of South China, Hengyang, China.
⁴ Department of Urology, Hunan Provincial People's Hospital, Changsha, China.
⁵ Department of Urology, The First Affiliated Hospital of Hunan Normal University, Hunan Normal University, Changsha, China.
⁶ Hunan Vocational and Technical College of Environmental Biology, Changsha, China.
⁷ Department of Urology, Xiangya Hospital, Central South University, Changsha, China. chenjinbo@csu.edu.cn.
⁸ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. chenjinbo@csu.edu.cn.
⁹ Department of Urology, Xiangya Hospital, Central South University, Changsha, China. fanbenyi2009@yeah.net.
¹⁰ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. fanbenyi2009@yeah.net.
¹¹ Department of Urology, Xiangya Hospital, Central South University, Changsha, China. dds15116217256@163.com.
¹² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. dds15116217256@163.com.

^# Contributed equally.

PMID: 39334304
PMCID: PMC11437728
DOI: 10.1186/s40364-024-00657-y

Abstract

Resistance to immunotherapy in bladder cancer has greatly limited its clinical application. Through single-cell sequencing, we determined that ACSM6, an oncogene that is highly expressed in bladder cancer, promotes the abilities of proliferation, cloning, migration, and invasion. The key point is that ACSM6 can also lead to a non-inflammatory immune microenvironment by inhibiting the chemotaxis and tumor killing ability of CD8⁺ T cells. Survival analysis revealed that high ACSM6 expression was associated with shorter overall survival in the immunotherapy cohort. In summary, ACSM6 is expected to become a novel biomarker for predict bladder cancer progression.

Keywords: ACSM6; Bladder cancer; Immunotherapy resistance; Non-inflammatory immune microenvironment; Tumor microenvironment.

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Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1**
ACSM6 mediates inhibitory tumor immune microenvironment in bladder cancer and leads to drug resistance in immunotherapy. **(A)** Xiangya Single cell cohort to illuminate ACSM6 high expression cells. Over-expression fold change has been verified with RT-qPCR **(B)** and Western blotting **(C)**. **(D)**. Cell proliferation assay. **(E)** Colony formation assay. **(F)** Transwell assay. **(G)** Wound healing assay. **(H)** Simple heat map to illuminate the impact of high expression of ACSM6 on immune function in TCGA and Xiangya cohorts. GSEA analysis of GO **(I)** and KEGG **(J)** in Xiangya cohort with high expression of ACSM6. **(K)** GO and KEGG pathways down-regulated after over-expression of ACSM6. **(L)** Schematic map of chemotaxis assay. **(M)** Cells differential fold change of chemotaxis assay. **(N)** Co-cultivation killing assay. **(O)** Over-expression of ACSM6 inhibits the fold change of TNF-α and IFN-γ in CD8⁺ T cells. **(P)** Flow cytometry analysis of the expression level of TNF-α and IFN-γ in CD8⁺ T cells. Multi-color immuno-fluorescence of inflamed **(Q)** and non-inflamed **(R)** tumor tissue. **(S)** Flow cytometry like analysis describes the co-localization relationship between ACSM6 and CD8⁺ T cells and it’s quantitative analysis **(T)**. Pairing statistics of ACSM6⁺/CK19⁺ cells and CD8⁺T cells **(U)**. Kaplan-Meier plotter interpret the high expression of ACSM6 shorten the OS of immunotherapy

See this image and copyright information in PMC

References

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Oncogenic ACSM6 impairs CD8⁺ T cell-based immune response in bladder cancer

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Oncogenic ACSM6 impairs CD8⁺ T cell-based immune response in bladder cancer

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Conflict of interest statement

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