Cd48, a member of the signaling lymphocytic activation molecule family, is a glycosyl-phosphatidyl-inositol (GPI)-anchored cell-surface protein of the CD2 family. It participates in adhesion and activation of immune cells, and functions as an adhesion and co-stimulatory molecule. CD48 binds to CD2, 2B4, and bacterial FimH, and is involved in multiple immune-related pathways [2,3,4]. It has a wide range of biological functions including pathogen recognition, cellular activation, and cytokine regulation, playing a crucial role in the immune system [5].

In hepatocellular carcinoma (HCC), GDF15 promotes the generation and function enhancement of regulatory T (Treg) cells via interacting with CD48 on T cells. Gene ablation of GDF15 in HCC can convert an immunosuppressive tumor microenvironment (TME) to an inflammatory state, suggesting CD48 may be a key receptor mediating the immunosuppressive effect of GDF15 in HCC [1]. In non-small-cell lung cancer (NSCLC), CD48-positive NSCLC cells are more susceptible to natural killer (NK) cell-mediated cytotoxicity, and CD48 may help stratify NSCLC patients potentially responsive to NK-cell therapy [6]. In autoimmune hepatitis type 1, serum CD48 (sCD48) levels are elevated and can predict histological inflammation and fibrosis, with hepatic CD48 expression also elevated in patients and decreased after treatment [7]. In glioma, CD48 is highly expressed during malignant progression. High-CD48 patients have a poor prognosis, and CD48 influences glioma purity, local immune cell subpopulations, and immune function. A checkpoint risk score including CD48 may help assess the role of checkpoints in glioma [8].

In conclusion, Cd48 is essential for immune cell adhesion and activation, playing a significant role in various diseases such as HCC, NSCLC, autoimmune hepatitis type 1, and glioma. Gene-knockout or-knockdown models in these disease contexts have revealed its role in immune-related processes, providing potential therapeutic targets and new insights into disease mechanisms.

References:

1. Wang, Zhaowei, He, Lei, Li, Weina, Zhang, Cun, Li, Meng. . GDF15 induces immunosuppression via CD48 on regulatory T cells in hepatocellular carcinoma. In Journal for immunotherapy of cancer, 9, . doi:10.1136/jitc-2021-002787. https://pubmed.ncbi.nlm.nih.gov/34489334/

2. Pahima, Hadas, Puzzovio, Pier Giorgio, Levi-Schaffer, Francesca. 2018. 2B4 and CD48: A powerful couple of the immune system. In Clinical immunology (Orlando, Fla.), 204, 64-68. doi:10.1016/j.clim.2018.10.014. https://pubmed.ncbi.nlm.nih.gov/30366105/

3. Elishmereni, Moran, Levi-Schaffer, Francesca. 2010. CD48: A co-stimulatory receptor of immunity. In The international journal of biochemistry & cell biology, 43, 25-8. doi:10.1016/j.biocel.2010.09.001. https://pubmed.ncbi.nlm.nih.gov/20833258/

4. McArdel, Shannon L, Terhorst, Cox, Sharpe, Arlene H. 2016. Roles of CD48 in regulating immunity and tolerance. In Clinical immunology (Orlando, Fla.), 164, 10-20. doi:10.1016/j.clim.2016.01.008. https://pubmed.ncbi.nlm.nih.gov/26794910/

5. Munitz, Ariel, Bachelet, Ido, Levi-Schaffer, Francesca. . CD48 as a novel target in asthma therapy. In Recent patents on inflammation & allergy drug discovery, 1, 9-12. doi:. https://pubmed.ncbi.nlm.nih.gov/19075961/

6. Park, Eun Jae, Jun, Hye Won, Na, Ik Ho, Hong, Jin Tae, Han, Sang-Bae. 2021. CD48-expressing non-small-cell lung cancer cells are susceptible to natural killer cell-mediated cytotoxicity. In Archives of pharmacal research, 45, 1-10. doi:10.1007/s12272-021-01365-z. https://pubmed.ncbi.nlm.nih.gov/34905179/

7. Hu, Mingli, You, Zhengrui, Li, You, Wang, Qixia, Ma, Xiong. 2022. Serum Biomarkers for Autoimmune Hepatitis Type 1: the Case for CD48 and a Review of the Literature. In Clinical reviews in allergy & immunology, 63, 342-356. doi:10.1007/s12016-022-08935-z. https://pubmed.ncbi.nlm.nih.gov/35657576/

8. Zou, Cunyi, Zhu, Chen, Guan, Gefei, Wu, Anhua, Cheng, Wen. 2019. CD48 is a key molecule of immunomodulation affecting prognosis in glioma. In OncoTargets and therapy, 12, 4181-4193. doi:10.2147/OTT.S198762. https://pubmed.ncbi.nlm.nih.gov/31213836/