S100a5, a member of the S100 family of calcium-binding proteins, contains EF-hand motifs and binds calcium ions. It is involved in various biological processes, and its interaction with the receptor for advanced glycation end-products (RAGE) may engage in diverse pathological processes [2,5,6,7]. S100a5 also plays a role in copper homeostasis and may be involved in inflammation and olfactory signaling [2,4].

In bladder carcinoma, S100a5 acts as an immunosuppressive factor. Its expression in malignant cells inhibits CD8+ T-cell recruitment by reducing pro-inflammatory chemokine secretion, and it also attenuates effector T-cell killing of cancer cells by suppressing CD8+ T-cell proliferation and cytotoxicity. Targeting S100a5 can enhance the efficacy of anti-PD-1 treatment by promoting CD8+ T-cell infiltration and cytotoxicity in vivo [1]. In WHO grade I meningiomas, S100a5 expression is associated with recurrence, with high-intensity staining either leading to no recurrence or later recurrence compared to low-intensity staining [3].

In summary, S100a5 has important functions in immune regulation and tumor-related processes. In bladder cancer, its role in immunosuppression makes it a potential target to enhance immunotherapy efficacy. In meningiomas, it serves as a recurrence-related marker. Understanding S100a5 through in vivo studies, such as potential KO/CKO mouse models, could further reveal its detailed mechanisms in these disease conditions, providing insights for new treatment strategies [1,3].

References:

1. Li, Huihuang, Chen, Jinbo, Li, Zhenghao, Hu, Jiao, Zu, Xiongbing. 2023. S100A5 Attenuates Efficiency of Anti-PD-L1/PD-1 Immunotherapy by Inhibiting CD8+ T Cell-Mediated Anti-Cancer Immunity in Bladder Carcinoma. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2300110. doi:10.1002/advs.202300110. https://pubmed.ncbi.nlm.nih.gov/37414584/

2. Wheeler, Lucas C, Harms, Michael J. 2017. Human S100A5 binds Ca2+ and Cu2+ independently. In BMC biophysics, 10, 8. doi:10.1186/s13628-017-0040-y. https://pubmed.ncbi.nlm.nih.gov/29201357/

3. Hancq, S, Salmon, I, Brotchi, J, Kiss, R, Decaestecker, C. . S100A5: a marker of recurrence in WHO grade I meningiomas. In Neuropathology and applied neurobiology, 30, 178-87. doi:. https://pubmed.ncbi.nlm.nih.gov/15043715/

4. Schäfer, B W, Fritschy, J M, Murmann, P, Heizmann, C W, Cox, J A. . Brain S100A5 is a novel calcium-, zinc-, and copper ion-binding protein of the EF-hand superfamily. In The Journal of biological chemistry, 275, 30623-30. doi:. https://pubmed.ncbi.nlm.nih.gov/10882717/

5. Kim, Iktae, Lee, Ko On, Yun, Young-Joo, Kim, Nak-Kyoon, Suh, Jeong-Yong. 2016. Biophysical characterization of Ca2+-binding of S100A5 and Ca2+-induced interaction with RAGE. In Biochemical and biophysical research communications, 483, 332-338. doi:10.1016/j.bbrc.2016.12.143. https://pubmed.ncbi.nlm.nih.gov/28017722/

6. Cho, Ching Chang, Chou, Ruey Hwang, Yu, Chin. 2016. Pentamidine blocks the interaction between mutant S100A5 and RAGE V domain and inhibits the RAGE signaling pathway. In Biochemical and biophysical research communications, 477, 188-94. doi:10.1016/j.bbrc.2016.06.041. https://pubmed.ncbi.nlm.nih.gov/27297108/

7. Bertini, Ivano, Das Gupta, Soumyasri, Hu, Xiaoyu, Parigi, Giacomo, Yuan, Jing. 2009. Solution structure and dynamics of S100A5 in the apo and Ca2+-bound states. In Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry, 14, 1097-107. doi:10.1007/s00775-009-0553-1. https://pubmed.ncbi.nlm.nih.gov/19536568/