CD8A, also known as cluster of differentiation 8 alpha, is a crucial gene associated with the T cytotoxic pathway. It codes for a subunit of the CD8 cell surface glycoprotein, which is primarily expressed on cytotoxic T lymphocytes (CTLs). CD8A-expressing CTLs play a pivotal role in the immune response by recognizing and eliminating virus-infected or cancerous cells. This is achieved through the interaction of CD8A with major histocompatibility complex class I (MHC-I) molecules on target cells, facilitating T-cell activation and cytotoxicity [4].

In various diseases, CD8A has shown significant implications. In bladder cancer, it was identified as a novel protective gene, and its low expression was linked to immunotherapeutic failure and poor survival in advanced patients receiving immunotherapy. A radiomics signature based on preoperative MRI features could predict CD8A expression, suggesting its potential as a biomarker for prognosis and immunotherapeutic response prediction [1]. In clear cell renal cell carcinomas (ccRCCs), single-cell sequencing detected enrichment of CD8A+ tissue-resident T cells in a patient responsive to immune checkpoint blockade (ICB), indicating its role in the immune landscape and therapy efficacy [2]. In bronchopulmonary dysplasia (BPD), CD8A expression was down-regulated, and it was closely associated with immune cell infiltration, especially T cells CD8 and neutrophil, making it a potential biomarker for BPD [3]. In breast cancer, CD8A was down-regulated in metastatic lesions, and its high expression in the immune microenvironment of metastatic triple-negative breast cancer (TNBC) was associated with a good prognosis [5]. Polymorphisms in the CD8A gene were associated with severity factors in chronic rhinosinusitis (CRS), suggesting its role in the development of refractory CRS [6]. Also, CD8A, along with IL7R and GZMA, may serve as potential molecular biomarkers for sepsis [7].

In conclusion, CD8A is essential for the function of cytotoxic T lymphocytes and plays a significant role in multiple disease conditions. Its expression levels and gene polymorphisms are associated with disease prognosis, immunotherapy response, and immune cell infiltration in various cancers, BPD, CRS, and sepsis. Research on CD8A using in vivo models, like the potential use of KO/CKO mouse models (although not directly mentioned in the provided references but inferred as valuable for further functional studies), could further elucidate its precise mechanisms in these diseases, potentially leading to new therapeutic strategies.

References:

1. Zheng, Zongtai, Guo, Yadong, Huang, Xiongsheng, Qiu, Xiaofu, Liu, Shenghua. 2022. CD8A as a Prognostic and Immunotherapy Predictive Biomarker Can Be Evaluated by MRI Radiomics Features in Bladder Cancer. In Cancers, 14, . doi:10.3390/cancers14194866. https://pubmed.ncbi.nlm.nih.gov/36230788/

2. Krishna, Chirag, DiNatale, Renzo G, Kuo, Fengshen, Chan, Timothy A, Hakimi, A Ari. 2021. Single-cell sequencing links multiregional immune landscapes and tissue-resident T cells in ccRCC to tumor topology and therapy efficacy. In Cancer cell, 39, 662-677.e6. doi:10.1016/j.ccell.2021.03.007. https://pubmed.ncbi.nlm.nih.gov/33861994/

3. Du, Yiting, Zuo, Limin, Xiong, Ying, Zou, Jun, Xu, Hong. 2023. CD8A is a Promising Biomarker Associated with Immunocytes Infiltration in Hyperoxia-Induced Bronchopulmonary Dysplasia. In Journal of inflammation research, 16, 1653-1669. doi:10.2147/JIR.S397491. https://pubmed.ncbi.nlm.nih.gov/37092130/

4. Kioussis, Dimitris, Ellmeier, Wilfried. . Chromatin and CD4, CD8A and CD8B gene expression during thymic differentiation. In Nature reviews. Immunology, 2, 909-19. doi:. https://pubmed.ncbi.nlm.nih.gov/12461564/

5. Chu, Jian, Tang, Shan, Li, Tangya, Fan, Huiwen. . The Role of CD8A in the Immune Microenvironment of Breast Cancer. In Frontiers in bioscience (Landmark edition), 29, 73. doi:10.31083/j.fbl2902073. https://pubmed.ncbi.nlm.nih.gov/38420798/

6. Alromaih, Saud, Mfuna-Endam, Leandra, Bosse, Yohan, Filali-Mouhim, Abdelali, Desrosiers, Martin. 2013. CD8A gene polymorphisms predict severity factors in chronic rhinosinusitis. In International forum of allergy & rhinology, 3, 605-11. doi:10.1002/alr.21174. https://pubmed.ncbi.nlm.nih.gov/23640800/

7. Li, Jin, Wang, Lantao, Yu, Bin, Su, Jie, Dong, Shimin. 2024. IL7R, GZMA and CD8A serve as potential molecular biomarkers for sepsis based on bioinformatics analysis. In Frontiers in immunology, 15, 1445858. doi:10.3389/fimmu.2024.1445858. https://pubmed.ncbi.nlm.nih.gov/39654893/