Xenograft cancer vaccines prepared from immunodeficient mice increase tumor antigen diversity and host T cell efficiency against colorectal cancers

Ke, Chiao-Hsu; Wang, Yushan; Chiang, Hou‐Yu; Wu, Hsin‐Yi; Liu, Wang-Jing; Huang, Chun-Yuan; Huang, Yuan-Li; Lin, Chen-Si

doi:10.1016/j.canlet.2021.11.012

Cited by 5 publications

(10 citation statements)

References 43 publications

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“…Furthermore, an exome sequence analysis revealed that tumors from RAG2 −/− mice, unlike those from WT mice, displayed elevated immunogenicity by determining the mutational landscape, in which a point mutation in Spectrin-β2, a neo-epitope, was identified [18]. Consistent with these publications, our previous study demonstrated similar findings: tumors arising in immunocompromised, i.e., NOD.CB17-Prkdcscid/NcrCrl (NOD.SCID), mice exhibited more malignant phenotypes and increased immunogenicity [14]. These results suggested that tumors derived from a defective immune system expressed a higher level of immunogenic tumor antigens.…”

Section: Introductionsupporting

confidence: 75%

“…Tumors downregulate their expressed antigens and the MHC complex, which the immune system can recognize, in order to evade immunosurveillance. When tumors are established in immunodeficient hosts, without immune recognition, they can progressively outgrow those developing in immunocompetent individuals [14,15]. With the consistent instability within tumors, the dysregulation of cell signaling, which manipulates cell proliferation, facilitates tumor development.…”

Section: Introductionmentioning

confidence: 99%

“…Tumors will change their traits within an immunocompromised host, constructing an environment that facilitates tumor progression and thereby increasing tumor immunogenicity [14,15]. For example, tumors originating from immunodeficient (RAG2 −/− ) mice were more capable of triggering an immune response, indicating that these tumors were more immunogenic than those in wild-type (WT) mice [17].…”

Section: Introductionmentioning

confidence: 99%

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Tumors Established in a Defective Immune Environment Reprogram the Oncogenic Signaling Pathways to Escalate Tumor Antigenicity

Ke,

Wu,

Wang

et al. 2024

Biomedicines

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Tumors developed in immunocompromised hosts are more immunogenic. However, few studies have addressed the potential mechanisms underlying the high immunogenicity of tumors found in a suppressed immune system. Therefore, we aimed to elucidate the impacts of the immune system on tumor behaviors and immunogenicity sculpting. A murine colorectal adenocarcinoma cell line, CT26wt, was administrated into immunocompetent (BALB/c) and immunocompromised (NOD.SCID) mice, respectively. On day 11, the CT26 cells slowly progressed in the NOD.SCID mice compared to the BALB/c mice. We then performed liquid chromatography–tandem mass spectrometry (LC-MS/MS) and analyzed the differentially expressed proteins (DEPs). The DEPs participated in numerous oncogenic pathways, PI3K/AKT/mTOR cell signaling, and the silencing of several tumor suppressors, such as PTEN and RBL1, during tumorigenesis. On day 34, the CT26/SCID tumors inversely became malignant counterparts; then the CT26/SCID tumors were harvested and re-inoculated into immunocompetent mice (CT26/SCID-Re tumors) to determine the immunogenicity. The CT26/SCID-Re tumor growth rate significantly decreased. Furthermore, increased infiltrations of dendritic cells and tumor-infiltrating T lymphocytes were found in the CT26/SCID-Re tumors. These findings suggest that immunogenic tumors might express multiple tumor rejection antigens, unlike wild-type tumors, and attract more immune cells, therefore decreasing the growth rate. Collectively, our study first revealed that in immunodeficient hosts, tumor suppressors were silenced and oncogenic signaling pathways were changed during the initial phase of tumor development. With tumor progression, the tumor antigens were overexpressed, exhibiting elevated immunogenicity. This study offers a hint on the mechanisms of tumorigenesis and provides a niche for investigating the interaction between host immunity and cancer development.

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Section: Introductionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tumors Established in a Defective Immune Environment Reprogram the Oncogenic Signaling Pathways to Escalate Tumor Antigenicity

Ke,

Wu,

Wang

et al. 2024

Biomedicines

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“…The digested peptides were extracted with acetonitrile containing 1% (v/v) formic acid by incubation at 37 °C for 15 min. This step was repeated twice, and the pooled extracts were vacuum dried and analyzed by LC–MS/MS 45 .…”

Section: Methodsmentioning

confidence: 99%

A structure of the relict phycobilisome from a thylakoid-free cyanobacterium

Jiang,

Wu,

Wang

et al. 2023

Nat Commun

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Phycobilisomes (PBS) are antenna megacomplexes that transfer energy to photosystems II and I in thylakoids. PBS likely evolved from a basic, inefficient form into the predominant hemidiscoidal shape with radiating peripheral rods. However, it has been challenging to test this hypothesis because ancestral species are generally inaccessible. Here we use spectroscopy and cryo-electron microscopy to reveal a structure of a “paddle-shaped” PBS from a thylakoid-free cyanobacterium that likely retains ancestral traits. This PBS lacks rods and specialized ApcD and ApcF subunits, indicating relict characteristics. Other features include linkers connecting two chains of five phycocyanin hexamers (CpcN) and two core subdomains (ApcH), resulting in a paddle-shaped configuration. Energy transfer calculations demonstrate that chains are less efficient than rods. These features may nevertheless have increased light absorption by elongating PBS before multilayered thylakoids with hemidiscoidal PBS evolved. Our results provide insights into the evolution and diversification of light-harvesting strategies before the origin of thylakoids.

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“…The result of protein sequences of TV NOS submitted to INTERPRO website. References [ 45 , 46 , 47 , 48 , 49 ] are cited in the Supplementary Materials.…”

mentioning

confidence: 99%

Innovative Hybrid-Alignment Annotation Method for Bioinformatics Identification and Functional Verification of a Novel Nitric Oxide Synthase in Trichomonas vaginalis

Lin

Shui

Huang

et al. 2022

Biology

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Both the annotation and identification of genes in pathogenic parasites are still challenging. Although, as a survival factor, nitric oxide (NO) has been proven to be synthesized in Trichomonas vaginalis (TV), nitric oxide synthase (NOS) has not yet been annotated in the TV genome. We developed a witness-to-suspect strategy to identify incorrectly annotated genes in TV via the Smith–Waterman and Needleman–Wunsch algorithms through in-depth and repeated alignment of whole coding sequences of TV against thousands of sequences of known proteins from other organisms. A novel NOS of TV (TV NOS), which was annotated as hydrogenase in the NCBI database, was successfully identified; this TV NOS had a high witness-to-suspect ratio and contained all the NOS cofactor-binding motifs (NADPH, tetrahydrobiopterin (BH4), heme and flavin adenine dinucleotide (FAD) motifs). To confirm this identification, we performed in silico modeling of the protein structure and cofactor docking, cloned the gene, expressed and purified the protein, performed mass spectrometry analysis, and ultimately performed an assay to measure enzymatic activity. Our data showed that although the predicted structure of the TV NOS protein was not similar to the structure of NOSs of other species, all cofactor-binding motifs could interact with their ligands with high affinities. We clearly showed that the purified protein had high enzymatic activity for generating NO in vitro. This study provides an innovative approach to identify incorrectly annotated genes in TV and highlights a novel NOS that might serve as a virulence factor of TV.

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Xenograft cancer vaccines prepared from immunodeficient mice increase tumor antigen diversity and host T cell efficiency against colorectal cancers

Cited by 5 publications

References 43 publications

Tumors Established in a Defective Immune Environment Reprogram the Oncogenic Signaling Pathways to Escalate Tumor Antigenicity

Tumors Established in a Defective Immune Environment Reprogram the Oncogenic Signaling Pathways to Escalate Tumor Antigenicity

A structure of the relict phycobilisome from a thylakoid-free cyanobacterium

Innovative Hybrid-Alignment Annotation Method for Bioinformatics Identification and Functional Verification of a Novel Nitric Oxide Synthase in Trichomonas vaginalis

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