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Cited by 49Cancer Immunotherapy and BiomarkersBladder and Urothelial Cancer TreatmentsS100 Proteins and Annexins

S100A5 Attenuates Efficiency of Anti‐PD‐L1/PD‐1 Immunotherapy by Inhibiting CD8+ T Cell‐Mediated Anti‐Cancer Immunity in Bladder Carcinoma

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Li, Huihuang, Chen, Jinbo, Li, Zhenghao, Chen, Minfeng, Ou, Zhenyu, Mo, Miao, Wang, Ruizhe, Tong, Shiyu +9 more·2023·Advanced Science
DOI 10.1002/advs.202300110PMC PMC10477882
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Abstract

Abstract Although immune checkpoint blockade (ICB) therapies have been approved for bladder cancer (BLCA), only a minority of patients respond to these therapies, and there is an urgent need to explore combined therapies. Systematic multi‐omics analysis identified S100A5 as a novel immunosuppressive target for BLCA. The expression of S100A5 in malignant cells inhibited CD8+ T cell recruitment by decreasing pro‐inflammatory chemokine secretion. Furthermore, S100A5 attenuated effector T cell killing of cancer cells by inhibiting CD8+ T cell proliferation and cytotoxicity. In addition, S100A5 acted as an oncogene, thereby promoting tumor proliferation and invasion. Targeting S100A5 synergized with the efficacy of anti‐PD‐1 treatment by enhancing infiltration and cytotoxicity of CD8+ T cells in vivo. Clinically, there was a spatially exclusive relationship between S100A5+ tumor cells and CD8+ T cells in tissue microarrays. Moreover, S100A5 negatively correlated with immunotherapy efficacy in our real‐world and several public immunotherapy cohorts. In summary, S100A5 shapes a non‐inflamed tumor microenvironment in BLCA by inhibiting the secretion of pro‐inflammatory chemokines and the recruitment and cytotoxicity of CD8+ T cells. Targeting S100A5 converts cold tumors into hot tumors, thus enhancing the efficacy of ICB therapy in BLCA.

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  • TBX3 expression is significantly higher in cancer tissues than in normal tissues in both the Xiangya cohort and the TCGA-BLCA cohort.

    “Based on bulk RNA-seq data, we found that TBX3 was expressed significantly higher in cancer tissues as compared to normal tissues in both the Xiangya cohort 34,38 (Figure 1A) and TCGA-BLCA cohort (Figure 1B).”

    From TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance (2025) · cites this paper as [34]

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Authors
Li, H., Chen, J., Li, Z., Chen, M., Ou, Z., Mo, M., Wang, R., Tong, S., Liu, P., Cai, Z., Zhang, C., Liu, Z., Deng, D., Liu, J., Cheng, C., Hu, J., & Zu, X.
Affiliations
Central South University (CN)
Corresponding author
  • Hu, Jiao
  • Zu, Xiongbing
ORCID
Venue
Advanced Science
Publisher
Wiley
Published
2023-07-06
Volume
10
Issue
25
Pages
e2300110-e2300110
ISSN
2198-3844 (ISSN-L)
DOI
10.1002/advs.202300110
PMC
PMC10477882
OpenAlex
W4383315962
Cited by
49
References
69
Citations by year
2026: 10 · 2025: 9 · 2024: 17 · 2023: 13
FWCI
5.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Advanced Science (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81873626, 81902592, 82070785, 82103639)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Surgery › Bladder and Urothelial Cancer Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
Keywords
bladder cancer, immune checkpoint blockade, anti-PD-1 therapy, PD-L1 blockade, CD8+ T cells, tumor-infiltrating lymphocytes, chemokine secretion, tumor microenvironment, immunosuppression, cold tumor to hot tumor conversion, T cell cytotoxicity, tumor cell proliferation and invasion, combination immunotherapy
MeSH terms
Urinary Bladder, Urinary Bladder Neoplasms, Carcinoma, Humans, Immunotherapy, CD8-Positive T-Lymphocytes, Tumor Microenvironment

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