Cbx3/HP1γ deficiency confers enhanced tumor-killing capacity on CD8+ T cells

Sun, Michael; Ha, Ngoc T; Pham, Duc-Hung; Frederick, Megan A.; Sharma, Bhuvanesh Kumar; Naruse, Chie; Asano, Masahide; Pipkin, Matthew E.; George, Rani E.; Thai, To‐Ha

doi:10.1038/srep42888

Cited by 20 publications

(20 citation statements)

References 39 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, NK and NKT cells are sensitive to various inhibitory molecules within the TME ( 93 ). Moreover, we show that the frequency of NK and NKT cells in NB tumors is low, and no differences are detected in tumors from wt or Cbx3 /HP1γ-deficient mice yet NB tumor growth is greatly abrogated in Cbx3 /HP1γ-deficient mice ( 70 ). Our findings imply that NK or NKT cells may not play an important role in controlling NB tumor growth.…”

Section: Adoptive Nk- and Natural Killer T (Nkt)-cell Therapymentioning

confidence: 84%

“…Our recent studies suggest that such an approach is attainable. We show that by targeting the histone reader Cbx3 /HP1γ, we can enhance the tumor killing capacity of effector CD8 + T cells ( 69 , 70 ). As a result, adoptive transfer of Cbx3 /HP1γ-deficient CD8 + effector T cells alone into wild type (wt) tumor-bearing mice greatly reduces NB growth.…”

Section: Adoptive T-cell Therapy (Act)mentioning

confidence: 92%

See 1 more Smart Citation

The State of Cellular Adoptive Immunotherapy for Neuroblastoma and Other Pediatric Solid Tumors

Thai

2017

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Research on adult cancer immunotherapy is proceeding at a rapid pace resulting in an impressive success rate exemplified by a few high profile cases. However, this momentum is not readily extended to pediatric immunotherapy, and it is not for lack of trying. Though reasons for the slower advance are not apparent, some issues can be raised. Pediatric cancer patients represent a distinct demographic group whose immune system is inherently different from that of mature adults. Treating pediatric patients with immunotherapy designed for adults may not yield objective clinical responses. Here, we will present an update on adoptive T-cell and natural killer-cell therapies for neuroblastoma and other childhood solid tumors. Additionally, we will delineate key differences between human fetal/neonatal and adult immune systems. We hope this will generate interests leading to the discussion of potential future directions for improving adoptive cancer immunotherapy for children.

show abstract

Section: Adoptive Nk- and Natural Killer T (Nkt)-cell Therapymentioning

confidence: 84%

Section: Adoptive T-cell Therapy (Act)mentioning

confidence: 92%

The State of Cellular Adoptive Immunotherapy for Neuroblastoma and Other Pediatric Solid Tumors

Thai

2017

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, CBX3/HP1γ was demonstrated to have novel function in the epigenetic regulation of both cell differentiation and cancer development in various types of cancers ( 10 ). In particular, Michael Su et al found that reducing the levels of Cbx3/HP1γ could enhance tumor-killing capacity on CD8+ T cells ( 32 ). Taken these findings together, we suppose that Cbx3/HP1γ serve as not only a novel cancer biomarker of high value in diagnosis and prognosis, but also an effective target for gene therapy against various human cancers.…”

Section: Discussionmentioning

confidence: 99%

CBX3/HP1γ is upregulated in tongue squamous cell carcinoma and is associated with an unfavorable prognosis

Zhang

et al. 2018

Exp Ther Med

View full text Add to dashboard Cite

Increased expression of CBX3/HP1γ, a core component of heterochromatin protein 1, has recently proved to be involved in human tumorigenesis and patient prognosis. The present study aimed to investigate the expression of CBX3/HP1γ and its clinicopathological significance in primary tongue squamous cell carcinoma (TSCC). Gene expression profiles of CBX3/HP1γ in TSCC from Oncomine database were analyzed. The expression of CBX3/HP1γ at protein level was measured using immunohistochemistry (IHC). The potential associations between CBX3/HP1γ expression and multiple clinicopathological parameters were estimated using the Chi square test. In addition, the effect of CBX3/HP1γ expression on patients' survival was further assessed by Kaplan-Meier and Cox regression analyses. The agreement of elevated CBX3/HP1γ expression was indicated in four datasets on the Oncomine database. Aberrant overexpression of CBX3/HP1γ was identified in TSCC tissues compared with cancer-adjacent normal tissue, which was significantly associated with cervical nodes metastasis (P=0.010) and clinical stage (P=0.025). Furthermore, patients with high CBX3/HP1γ expression exhibited a reduced survival compared with those with low expression (Log-rank test, P=0.004). Univariate and multivariate Cox regression analysis suggested that the expression status of CBX3/HP1γ could be regarded as an independent prognostic factor for TSCC patients (HR=2.461; 95% CI=1.128–5.370; P=0.024). The present study indicated that aberrant overexpression of Cbx3/HP1γ was associated with cervical nodes metastasis and unfavorable survival in TSCC. These findings suggest that CBX3/HP1γ may serve an important role in tongue tumorigenesis and may be a valuable candidate diagnostic and prognostic marker for TSCC patients.

show abstract

“…Currently, many different approaches exist, which do not fullfill this set of criteria. The vast majority of them, including DNA 8,9 -and RNA [10][11][12][13] -based PCR and reverse transcription quantitative real-time PCR (RT-qPCR), species-specific transcriptome [14][15][16][17][18][19][20] and proteome 21,22 analyses as well as flow cytometry [23][24][25] , are molecular profiling approaches which require tissue dissociation or lysis and do not address host contribution in situ on a single cell level. To investigate the unperturbed interaction between the tumor and its microenvironment, the use of genetically modified cells or mouse models expressing fluorescent reporter proteins [26][27][28][29][30] might want to be avoided.…”

Section: Comparison With Existing Approachesmentioning

confidence: 99%

An antibody-based approach for the in situ evaluation of mouse contribution in human stem cell-derived xenografts

Hengstschläger¹,

Rosner²

2018

Protocol Exchange

View full text Add to dashboard Cite

Studying human xenografts in mice is a widely used and powerful approach in both, stem cell and cancer research. Since the indispensible role of invaded host cells for teratoma respectively tumor development became evident, sensitive methods to detect mouse infiltration are in demand. For this purpose, in situ-labeling is generally preferred since it allows to draw valuable conclusions on host cell properties such as cell morphology, location and structural assembly. Unlike existing approaches, which employ species-specific antibodies to detect distinct cell types such as endothelial cells, immune cells or fibroblasts, our protocol exploits the species-specific detection of a proven housekeeping protein to visualize the microenvironment as a whole. So far undescribed, this 24-hours fluorescent immunohistochemistry (IHC) protocol enables the detection of mouse cells irrespective of a particular cell type or subpopulation and thus allows to draw are more comprehensive picture of host cell contribution in a single detection step.

show abstract

Cbx3/HP1γ deficiency confers enhanced tumor-killing capacity on CD8+ T cells

Cited by 20 publications

References 39 publications

The State of Cellular Adoptive Immunotherapy for Neuroblastoma and Other Pediatric Solid Tumors

The State of Cellular Adoptive Immunotherapy for Neuroblastoma and Other Pediatric Solid Tumors

CBX3/HP1γ is upregulated in tongue squamous cell carcinoma and is associated with an unfavorable prognosis

An antibody-based approach for the in situ evaluation of mouse contribution in human stem cell-derived xenografts

Contact Info

Product

Resources

About