Itgal, also known as Integrin subunit alpha L, encodes an integrin component of LFA-1 and is a membrane receptor molecule widely expressed on leukocytes. It plays a key role in the interaction between white blood cells and other cells, and is involved in immune-related pathways [1,2,3,5,6,7]. Genetic models, such as gene knockout mouse models, can be valuable for studying its functions.

In various cancers, Itgal shows different expression patterns and associations with prognosis and immune cell infiltration. In non-small-cell lung cancer (NSCLC), Itgal was downregulated in tumor tissues compared to paracancerous tissues, and low expression was associated with poor prognosis. Higher Itgal expression was related to increased infiltration of CD8+ T cells, CD68+ macrophages, CD4+ T cells, and CD20+ B cells, and was also associated with better outcomes in patients with immune checkpoint inhibitor therapy [1]. In acute myeloid leukemia, Itgal was highly expressed and associated with poor prognosis, and was related to the number of myeloid-derived suppressor cells (MDSCs) and cytokine production [2]. In gastric cancer, Itgal expression was increased in cancer samples, and was related to poor survival and various immune cell infiltrates [3]. In melanoma, its role in immune infiltration and prognosis was investigated [4]. In lung adenocarcinoma, high Itgal expression was associated with better survival, and Itgal suppressed malignant progression and affected the tumor microenvironment [6]. In contrast, in NSCLC, low Itgal expression was related to poorer prognosis and increased malignancy, and its co-expressed genes were associated with immune-associated signaling pathways [7]. In murine low-grade glioma, Itgal/CD11A was identified as a critical microglia regulator, and antibody-mediated CD11a inhibition reduced mouse Nf1 LGG growth in vivo [8].

In conclusion, Itgal is crucial for leukocyte-cell interactions and immune-related functions. Model-based research, especially gene knockout mouse models as in the case of murine low-grade glioma, has revealed its roles in cancer-related processes such as prognosis, immune cell infiltration, and tumor growth regulation, providing insights into potential therapeutic strategies for various cancers.

References:

1. Zhang, Ruihao, Zhu, Guangsheng, Li, Zaishan, Liu, Hongyu, Chen, Jun. 2024. ITGAL expression in non-small-cell lung cancer tissue and its association with immune infiltrates. In Frontiers in immunology, 15, 1382231. doi:10.3389/fimmu.2024.1382231. https://pubmed.ncbi.nlm.nih.gov/38646528/

2. Li, Ran, Wu, Xiaolu, Xue, Kai, Li, Junmin. 2022. ITGAL infers adverse prognosis and correlates with immunity in acute myeloid leukemia. In Cancer cell international, 22, 268. doi:10.1186/s12935-022-02684-x. https://pubmed.ncbi.nlm.nih.gov/35999614/

3. Zhang, Junchang, Wang, Han, Yuan, Cheng, Zhang, Changhua, He, Yulong. 2022. ITGAL as a Prognostic Biomarker Correlated With Immune Infiltrates in Gastric Cancer. In Frontiers in cell and developmental biology, 10, 808212. doi:10.3389/fcell.2022.808212. https://pubmed.ncbi.nlm.nih.gov/35399517/

4. Deng, TengFei, Wang, Chaoyong, Gao, Cong, Zhang, Qiang, Guo, Jun. 2023. ITGAL as a prognostic biomarker correlated with immune infiltrates in melanoma. In Frontiers in oncology, 13, 1181537. doi:10.3389/fonc.2023.1181537. https://pubmed.ncbi.nlm.nih.gov/37388230/

5. Lin, Fengjie, Yang, Hanxuan, Huang, Zongwei, Ye, Yunbin, Qiu, Sufang. 2024. Magnesium-related gene ITGAL: a key immunotherapy predictor and prognostic biomarker in pan-cancer. In Frontiers in pharmacology, 15, 1464830. doi:10.3389/fphar.2024.1464830. https://pubmed.ncbi.nlm.nih.gov/39605903/

6. Xiao, Zengtuan, Nian, Zhe, Zhang, Mengzhe, Liu, Zhe, Zhang, Zhenfa. . Integrated analysis highlights the significance role of ITGAL in lung adenocarcinoma. In Journal of cellular and molecular medicine, 28, e18289. doi:10.1111/jcmm.18289. https://pubmed.ncbi.nlm.nih.gov/38613346/

7. Wang, Qiang, Xiao, GuangJun, Li, Na, Jiang, Xiulin, Li, Chunhong. 2023. lncRNA PCBP1-AS1 mediated downregulation of ITGAL as a prognostic biomarker in lung adenocarcinoma. In Aging, 15, 4510-4523. doi:10.18632/aging.204756. https://pubmed.ncbi.nlm.nih.gov/37256932/

8. De Andrade Costa, Amanda, Chatterjee, Jit, Cobb, Olivia, Dahiya, Sonika, Gutmann, David H. . RNA sequence analysis reveals ITGAL/CD11A as a stromal regulator of murine low-grade glioma growth. In Neuro-oncology, 24, 14-26. doi:10.1093/neuonc/noab130. https://pubmed.ncbi.nlm.nih.gov/34043012/