Is Candida albicans an opportunistic oncogenic pathogen?

Sultan, Ahmed S.; Theofilou, Vasileios Ionas; Alfaifi, Areej; Montelongo-Jauregui, Daniel; Jabra-Rizk, Mary-Ann

doi:10.1371/journal.ppat.1010413

Cited by 9 publications

(9 citation statements)

References 40 publications

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“…Recently, our lab identified the Agglutinin-Like Sequences (ALS) protein family as a novel fungal ligand for TIGIT in both human and mice 10 . Candida albicans can also be found in tumors such as oral 31 , colon cancer 32 as well as other forms of cancer 33 . It is currently unknown whether the Candida -TIGIT interactions within the tumors will be beneficial in the tumor microenvironment and this issue can be investigated in the future using our TIGIT KO mice.…”

Section: Discussionmentioning

confidence: 99%

Studying TIGIT activity against tumors through the generation of knockout mice

Rishiq,

Bsoul,

Pick

et al. 2023

OncoImmunology

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The use of antibodies to block inhibitory receptors, primarily anti-PD1 and CTLA4 (known as checkpoint therapy) revolutionized cancer treatment. However, despite these successes, the majority of cancer patients do not respond to the checkpoint treatment, emphasizing the need for development of additional therapies, which are based on other inhibitory receptors. Human TIGIT is an inhibitory receptor expressed by Natural Killer (NK) and T cells and is mainly known to interact with PVR, Nectin-2, Nectin-3, and Nectin-4. Whether mouse TIGIT interacts with all of these ligands is still unclear. Additionally, the in vivo function of TIGIT against tumors is not completely understood. Here, we demonstrate that mouse TIGIT interacts with and is inhibited by mPVR only. Using CRISPR-Cas9 technology, we generated TIGIT-deficient mice and demonstrated that NK cell cytotoxicity and degranulation against two tumor types were lower in WT mice when compared to the TIGIT KO mice. Moreover, in vivo tumor progression was slower in TIGIT KO than in WT mice. Taken together, our data established that mTIGIT has only one ligand, PVR, and that in the absence of TIGIT tumors are killed better both in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Studying TIGIT activity against tumors through the generation of knockout mice

Rishiq,

Bsoul,

Pick

et al. 2023

OncoImmunology

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“…There has been increased support for microRNA therapeutics in solid organ transplantation, including kidney ( Wilflingseder et al, 2015 ; Jin et al, 2017 ; Ledeganck et al, 2019 ), lung ( Benazzo et al, 2022 ), and heart transplantation ( Hamdorf et al, 2017 ). Candida albicans have been linked to cancerous processes by taking advantage of the compromised immune system ( Ramirez-Garcia et al, 2016 ; Chung et al, 2017 ; Sultan et al, 2022 ). Our PPI network analysis identified four hub genes ( SLC2A1, VEGFA , JUN , and PTGS2 ) enriched in the cancer-related pathways.…”

Section: Discussionmentioning

confidence: 99%

Coexpression network analysis of human candida infection reveals key modules and hub genes responsible for host-pathogen interactions

Naik

Mohammed

2022

Front. Genet.

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Invasive fungal infections are a significant reason for morbidity and mortality among organ transplant recipients. Therefore, it is critical to investigate the host and candida niches to understand the epidemiology of fungal infections in transplantation. Candida albicans is an opportunistic fungal pathogen that causes fatal invasive mucosal infections, particularly in solid organ transplant patients. Therefore, identifying and characterizing these genes would play a vital role in understanding the complex regulation of host-pathogen interactions. Using 32 RNA-sequencing samples of human cells infected with C. albicans, we developed WGCNA coexpression networks and performed DESeq2 differential gene expression analysis to identify the genes that positively correlate with human candida infection. Using hierarchical clustering, we identified 5 distinct modules. We studied the inter- and intramodular gene network properties in the context of sample status traits and identified the highly enriched genes in the correlated modules. We identified 52 genes that were common in the most significant WGCNA turquoise module and differentially expressed genes in human endothelial cells (HUVEC) infection vs. control samples. As a validation step, we identified the differentially expressed genes from the independent Candida-infected human oral keratinocytes (OKF6) samples and validated 30 of the 52 common genes. We then performed the functional enrichment analysis using KEGG and GO. Finally, we performed protein-protein interaction (PPI) analysis using STRING and CytoHubba from 30 validated genes. We identified 8 hub genes (JUN, ATF3, VEGFA, SLC2A1, HK2, PTGS2, PFKFB3, and KLF6) that were enriched in response to hypoxia, angiogenesis, vasculogenesis, hypoxia-induced signaling, cancer, diabetes, and transplant-related disease pathways. The discovery of genes and functional pathways related to the immune system and gene coexpression and differential gene expression analyses may serve as novel diagnostic markers and potential therapeutic targets.

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“…It is well known that fungi are a small part of the oral microbiota; however, these opportunistic pathogens have been linked to carcinogenesis. 40,41 Candida albicans (C. albicans) is well-known as the predominant species in the oral cavity and involved in oral cancer development. The mechanisms by which C. albicans may initiate or promote oral carcinogenesis are still not well-established.…”

Section: Discussionmentioning

confidence: 99%

“…Fifth, the influence of Candida infection on the tumor suppressor gene p53, cell proliferation nuclear antigen Ki-67, and (COX-2) expression that is related to malignant transformation through the upregulation of inflammatory and epithelial proliferatition. 40,[42][43][44] These possible mechanisms may provide our understanding of the oral cancer development associated with fungal dysbiosis.…”

Section: Discussionmentioning

confidence: 99%

Oral microbiota in oral cancer patients and healthy individuals: A scoping review

Sufiawati

Piliang²,

Ramamoorthy³

2022

Dent. J. (Majalah Kedokt. Gigi)

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Background: Oral microbiota has been suggested to have a role in the etiopathogenesis of oral cancer; however, the oral microbiota diversity in patients with oral cancer compared to healthy individuals remains unclear. Purpose: This scoping review aimed to provide an overview of the current evidence regarding the oral microbiota composition colonized in oral cancer patients and its comparison with healthy individuals. Reviews: This study was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Eligible studies were searched in PubMed, Scopus, Web of Science, and ScienceDirect databases from January 2015 to March 2022. A total of 20 relevant studies were included according to the inclusion and exclusion criteria, including 14 cross-sectional studies and 6 cohort studies. All studies have identified various oral bacteria, but only one study has detected viruses and parasites diversity. A variety of oral microbiota found were 6 phyla of bacteria, 6 phyla of viruses, 7 phyla of fungi, and 7 phyla of parasitic. Seventeen studies proved that oral microbiota compositions were statistically significant differences compared to healthy controls, but not in 3 studies. Conclusion: The majority of studies showed various oral bacteria in oral cancer patients which were statistically significant difference compared to healthy controls. This study indicates the need for more research to evaluate viruses and parasites composition and diversity in oral cancer patients. Moreover, future research should focus to clarify whether the changes of oral microbial composition as a community may play a critical role in the etiopathogenesis of oral cancer.

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Is Candida albicans an opportunistic oncogenic pathogen?

Cited by 9 publications

References 40 publications

Studying TIGIT activity against tumors through the generation of knockout mice

Studying TIGIT activity against tumors through the generation of knockout mice

Coexpression network analysis of human candida infection reveals key modules and hub genes responsible for host-pathogen interactions

Oral microbiota in oral cancer patients and healthy individuals: A scoping review

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