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The SNP rs755622 is associated with immune activation in Glioblastoma

ABSTRACT: Intratumoral heterogeneity is a defining hallmark of glioblastoma, driving drug resistant and ultimately recurrence. Many somatic drivers of microenvironmental change have been shown to affect this heterogeneity and ultimately treatment response. However, little is known about how germline mutations effect the tumoral microenvironment. Here, we find that the single-nucleotide polymorphism (SNP) rs755622 in promoter of the cytokine macrophage migration inhibitory factor (MIF), is associated with increased leukocyte infiltration in glioblastoma. Furthermore, we identified an association between rs755622 and lactotransferrin expression, which could also be used as a biomarker for immune-infiltrated tumors. These findings demonstrate that a germline SNP in the promoter region of MIF may impact the immune microenvironment and further reveals a link between lactotransferrin and immune activation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE232434 | GEO | 2023/05/12

REPOSITORIES: GEO

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Project description:Despite the demonstrated efficacy of immune checkpoint blockade therapies in various tumors, their efficacy in cervical cancer is limited by factors such as the need for positive PD-L1 expression and the development of drug resistance. A crucial pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF), is highly expressed in various cancers and contributes to tumor progression by regulating inflammatory responses and the tumor microenvironment. The present study aimed to explore the role of macrophage migration inhibitory factors in cervical squamous cell carcinoma (CSCC) recurrence and metastasis. Western blotting, reverse transcription quantitative PCR, cell-counting kit 8 assay, flow cytometry, and ELISA were used to investigate the effects of MIF on CSCC progression and formation of inflammasomes. Transcriptome and proteome sequencing were combined to screen for key effector proteins of MIF. Moreover, in vitro co-culture experiments, Transwell assays, and flow cytometry were used to evaluate the roles of MIF and TSC22 domain family protein 3 (TSC22D3) as inflammatory tumor-promoting factors in macrophage recruitment and polarization induction. The results indicated that MIF was highly expressed in CSCC with lymph node metastasis, positively correlated with cervical cancer stage, and associated with poor prognosis. MIF was found to promote CSCC progression and linked to inflammasome activation. Multi-omics screening results indicated that TSC22D3 may be a crucial interacting gene of MIC. Moreover, MIF and TSC22D3 could facilitate inflammasome activation, macrophage recruitment, and M2 polarization. Therefore, MIF and TSC22D3 can induce macrophage infiltration in cervical cancer lesions and affect the tumor microenvironment by polarizing macrophages toward the M2 phenotype, promoting CSCC progression. This study highlights the potential of targeting the MIF-TSC22D3 axis as a novel therapeutic strategy and offering a promising avenue for improving the efficacy of immunotherapy in treatin

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The SNP rs755622 is associated with immune activation in Glioblastoma

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