Comparative transcriptomic profiling in HPV-associated cervical carcinogenesis: Implication of MHC class II and immunoglobulin heavy chain genes

Balasubramaniam, Shandra Devi; Wong, Kah Keng; Oon, Chern Ein; Balakrishnan, Venugopal; Kaur, Gurjeet

doi:10.1016/j.lfs.2020.118026

Cited by 9 publications

(10 citation statements)

References 32 publications

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“…37 Meanwhile, the contradictory changing trend of neutrophils in our study remaining further explored by enlarging the sample numbers. Further, we found MHC class II genes associated with upregulated function from normalcy to HSIL supported by a previous study, 39 and interferon-γ response was updated from normalcy to LSIL and HSIL. It is widely acknowledged that the innate cells recognized foreign antigens by kinds of receptors, including the Toll-like receptors (TLRs).…”

Section: Discussionsupporting

confidence: 88%

“…Activated TLRs on APCs can trigger downstream signaling events leading to the expression of inflammatory cytokines and chemokines encompassing the interferon‐γ 40 . This production of inflammatory cytokines (e.g., IFN‐γ secreted by NK cells or Th1 cells) contributes to upregulate the expression of the MHC II complex on CD4 + T cells, annotating the malignant transformation from immunogenic to tolerogenic in the HSIL stage 39 . To sum up, the cytotoxic immune subpopulation exists decreasing abundance along with cervical tumorigenesis, and HSIL is the turning point during cervical carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

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The immune landscape during the tumorigenesis of cervical cancer

Wang

Zhang

et al. 2021

Cancer Medicine

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

The immune landscape during the tumorigenesis of cervical cancer

Wang

Zhang

et al. 2021

Cancer Medicine

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“…As the disease progresses to HGCIN and SCC, increased synthesis of HLA-DRA protein recruits immune support via CD4+ T cells, leading to more favourable CD8+ T-cells responses and thus preventing tumour invasion. This finding parallels a previous study using the same sample cohort that revealed deregulation of the immune-related genes, including MHC II and immunoglobulin heavy chain genes in the progression from LGCIN to HGCIN and SCC [32].…”

Section: Discussionsupporting

confidence: 90%

CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy

et al. 2022

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Background and Objectives: Abnormal expressions of CD74 and human leukocyte antigen-DR alpha (HLA-DRA) have been reported in various cancers, though their roles in cervical cancer remain unclear. This study aimed to evaluate the gene and protein expressions of CD74 and HLA-DRA in the progression from normal cervix to precancerous cervical intraepithelial neoplasia (CIN) and finally to squamous cell carcinoma (SCC). Materials and Methods: The gene expression profiles of CD74 and HLA-DRA were determined in formalin-fixed paraffin-embedded tissues, with three samples each from normal cervixes, human papillomavirus type 16/18-positive, low-grade CIN (LGCIN), high-grade CIN (HGCIN), and squamous cell carcinoma (SCC) using Human Transcriptome Array 2.0. Immunohistochemical expression of the proteins was semi-quantitatively assessed in another cohort of tissue microarray samples comprising 7 normal cervix cases, 10 LGCIN, 10 HGCIN, and 95 SCC. Results: The transcriptomics profile and proteins’ expression demonstrated similar trends of upregulation of CD74 and HLA-DRA from normal cervix to CIN and highest in SCC. There was a significant difference in both proteins’ expression between the histological groups (p = 0.0001). CD74 and HLA-DRA expressions were significantly associated with CIN grade (p = 0.001 and p = 0.030, respectively) but not with the subjects’ age or SCC stage. Further analysis revealed a positive correlation between CD74 and HLA-DRA proteins. Conclusions: CD74 appears to promote cervical carcinogenesis via oncogenic signalling mechanisms and may serve as a potential antitumour target. Additionally, the upregulation of HLA-DRA, often associated with stronger immunogenicity, could be a promising biomarker for developing immunotherapies.

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“…Balasubramaniam et. al, show that MHC-II genes were significantly up-regulated in HPV-associated cervical carcinogenesis (26). Contrary to this, a study on lung cancer reports significant down-regulation of MHC-II in tumour cells (27).…”

Section: Discussionmentioning

confidence: 99%

MHC-II molecules present RhoC-derived peptides on the surface of tumour cells

Thomas

2022

Preprint

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RhoC is an important regulator of metastasis and tumour progression across various tumour models. Since RhoC has been found to have no major contribution towards normal embryogenic development, it has emerged as a suitable therapeutic target for effective cancer treatment. Recent evidence has shown that Rho-based peptide vaccines have favourable outcomes in prostate cancer patients, by bringing about activation of CD4+ T-cells. Antigen presentation on the surface of cells is brought about by the MHC-I/MHC-II complex. This work provides conclusive evidence to show that the seemingly cytosolic protein, RhoC, is in fact, present on the surface of tumour cells. This report goes on to prove that the presentation of RhoC peptides is brought about in association with MHC-II, becoming the first piece of scientific evidence to report this phenomenon.

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Comparative transcriptomic profiling in HPV-associated cervical carcinogenesis: Implication of MHC class II and immunoglobulin heavy chain genes

Cited by 9 publications

References 32 publications

The immune landscape during the tumorigenesis of cervical cancer

The immune landscape during the tumorigenesis of cervical cancer

CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy

MHC-II molecules present RhoC-derived peptides on the surface of tumour cells

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