ITGAL as a prognostic biomarker correlated with immune infiltrates in melanoma

Deng, Tengfei; Wang, Chaoyong; Gao, Cong; Zhang, Qiang; Guo, Jun

doi:10.3389/fonc.2023.1181537

Cited by 1 publication

(1 citation statement)

References 49 publications

(51 reference statements)

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“…Upregulation of ITGAL expression was strongly associated with immunomodulators, chemokines, and levels of CD8+ T cells, CD4+ T cells, B cells, monocytes, neutrophils, macrophages, T cells, natural killer (NK) cells, and myeloid dendritic cell infiltration in gastric adenocarcinomas (STAD). Further, some studies indicate that ITGAL might play a key role in cancer growth and transformation, making it a potentially useful target in the treatment of a wide variety of cancers (15)(16)(17). The main effect of resveratrol on NSCLC treatment may be related to immune signaling pathways, according to a mechanistic study of resveratrol in NSCLC (18).…”

Section: Introductionmentioning

confidence: 99%

ITGAL expression in non-small-cell lung cancer tissue and its association with immune infiltrates

Zhang,

Zhu,

et al. 2024

Front. Immunol.

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BackgroundIntegrin subunit alpha L (ITGAL) 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. There was a significant correlation between the expression of ITGAL and the tumor microenvironment in a number of cancers. However, experimental studies targeting ITGAL and immune cell infiltration in non-small-cell lung cancer (NSCLC) and the response to immune checkpoint inhibitor therapy are lacking.MethodsData were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases to explore the relationship between ITGAL expression and prognosis, as well as the immune cell infiltration in patients with NSCLC. In addition, immunohistochemical staining for ITGAL and multiplex immunofluorescence (mIF) staining for ITGAL, CD20, CD68, CD4, and CD8 from tissue microarrays containing 118 tumor tissues and paired paracancerous tissues from patients with NSCLC were performed. The correlation between ITGAL expression and clinical factors, as well as the immunophenotypes of tumor-infiltrating immune cells, were also analyzed.ResultsIn NSCLC tumor tissues, ITGAL was downregulated compared with matched paracancerous tissues, and low ITGAL expression was associated with a poor prognosis of NSCLC patients. Subsequently, immunohistochemistry results for tissue microarray showed that ITGAL expression was mainly elevated in tumor stroma and areas with highly infiltrated immune cells. ITGAL expression was higher in paracancerous tissues than tumor tissues. Furthermore, mIF results indicated that the patients with ITGAL-high expression tend had significantly higher CD8+ T cells, CD68+ macrophages, CD4+ T cells, and CD20+ B cells infiltration in their tumor tissues. Immunophenotypes were classified into three categories, that is deserted, excluded, and inflamed types, according to each kind of immune cell distribution in or around the cancer cell nest. MIF results showed that ITGAL expression level was correlated with the immunophenotypes. Furthermore, ITGAL expression was associated with the prognosis of NSCLC in patients with immune checkpoint inhibitor therapy and the patients with high ITGAL expression tends have better outcomes.ConclusionsITGAL may be used as a biomarker for assessing the immune microenvironment in patients with NSCLC.

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