Transcriptional signature of CD56bright NK cells predicts favourable prognosis in bladder cancer
Human natural killer (NK) cells can be sub-divided into two functional subsets but the clinical significance of these CD56bright and CD56dim NK cells in anti-tumour immunity remains largely unexplored. We determined the relative abundances of gene signatures for CD56bright and CD56dim NK cells along...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1474652/full |
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| author | Md Abdullah Al Kamran Khan Alexander James Sedgwick Yuhan Sun Julian P. Vivian Julian P. Vivian Julian P. Vivian Alexandra J. Corbett Riccardo Dolcetti Riccardo Dolcetti Riccardo Dolcetti Theo Mantamadiotis Theo Mantamadiotis Stefano Mangiola Stefano Mangiola Stefano Mangiola Alexander David Barrow |
| author_facet | Md Abdullah Al Kamran Khan Alexander James Sedgwick Yuhan Sun Julian P. Vivian Julian P. Vivian Julian P. Vivian Alexandra J. Corbett Riccardo Dolcetti Riccardo Dolcetti Riccardo Dolcetti Theo Mantamadiotis Theo Mantamadiotis Stefano Mangiola Stefano Mangiola Stefano Mangiola Alexander David Barrow |
| author_sort | Md Abdullah Al Kamran Khan |
| collection | DOAJ |
| description | Human natural killer (NK) cells can be sub-divided into two functional subsets but the clinical significance of these CD56bright and CD56dim NK cells in anti-tumour immunity remains largely unexplored. We determined the relative abundances of gene signatures for CD56bright and CD56dim NK cells along with 3 stromal and 18 other immune cell types in the patient tumour transcriptomes from the cancer genome atlas bladder cancer dataset (TCGA-BLCA). Using this computational approach, CD56bright NK cells were predicted to be the more abundant tumour-infiltrating NK subset which was also associated with improved patient prognosis. A similar favorable survival trend was projected using gene signatures for mature myeloid dendritic cells (mDC) and CD8+ effector memory T cells (TEM) and unveiled a potential CD56bright NK-mDC-CD8+T cell crosstalk in the BLCA tumour microenvironment. Expression of transcripts encoding the activating NK cell receptors, NKG2D, NKp44, CD2, and CD160, showed positive survival trends in combination with CD56bright NK cell infiltration. Transcription factors including HOBIT, IRF3, and STAT2 were also correlated with CD56bright NK cell abundance. Additionally, a HOBIT-dependent tissue-residency program correlated with the CD56bright NK and CD8+ TEM cell signatures was found to be associated with favourable BLCA patient survival. Overall, our study highlights the significance of CD56bright NK cells in BLCA patient prognosis. Our findings facilitate a better understanding of the NK cell anti-tumour responses that may ultimately lead to the development of promising NK and T cell-based therapies for BLCA. |
| format | Article |
| id | doaj-art-fb842cefac9a4eed84af998a19ba05b9 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-fb842cefac9a4eed84af998a19ba05b92025-01-14T05:10:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14746521474652Transcriptional signature of CD56bright NK cells predicts favourable prognosis in bladder cancerMd Abdullah Al Kamran Khan0Alexander James Sedgwick1Yuhan Sun2Julian P. Vivian3Julian P. Vivian4Julian P. Vivian5Alexandra J. Corbett6Riccardo Dolcetti7Riccardo Dolcetti8Riccardo Dolcetti9Theo Mantamadiotis10Theo Mantamadiotis11Stefano Mangiola12Stefano Mangiola13Stefano Mangiola14Alexander David Barrow15Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaDepartment of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaDepartment of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaSt. Vincent’s Institute of Medical Research, Melbourne, VIC, AustraliaDepartment of Medicine, The University of Melbourne, Melbourne, VIC, AustraliaAustralian Catholic University, Melbourne, VIC, AustraliaDepartment of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaDepartment of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaPeter MacCallum Cancer Centre, Melbourne, VIC, AustraliaSir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, AustraliaDepartment of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaDepartment of Surgery, Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, AustraliaSouth Australian immunoGENomics Cancer Institute, The University of Adelaide, Adelaide, SA, AustraliaDivision of Bioinformatics, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia0Department of Medical Biology, University of Melbourne, Parkville, VIC, AustraliaDepartment of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaHuman natural killer (NK) cells can be sub-divided into two functional subsets but the clinical significance of these CD56bright and CD56dim NK cells in anti-tumour immunity remains largely unexplored. We determined the relative abundances of gene signatures for CD56bright and CD56dim NK cells along with 3 stromal and 18 other immune cell types in the patient tumour transcriptomes from the cancer genome atlas bladder cancer dataset (TCGA-BLCA). Using this computational approach, CD56bright NK cells were predicted to be the more abundant tumour-infiltrating NK subset which was also associated with improved patient prognosis. A similar favorable survival trend was projected using gene signatures for mature myeloid dendritic cells (mDC) and CD8+ effector memory T cells (TEM) and unveiled a potential CD56bright NK-mDC-CD8+T cell crosstalk in the BLCA tumour microenvironment. Expression of transcripts encoding the activating NK cell receptors, NKG2D, NKp44, CD2, and CD160, showed positive survival trends in combination with CD56bright NK cell infiltration. Transcription factors including HOBIT, IRF3, and STAT2 were also correlated with CD56bright NK cell abundance. Additionally, a HOBIT-dependent tissue-residency program correlated with the CD56bright NK and CD8+ TEM cell signatures was found to be associated with favourable BLCA patient survival. Overall, our study highlights the significance of CD56bright NK cells in BLCA patient prognosis. Our findings facilitate a better understanding of the NK cell anti-tumour responses that may ultimately lead to the development of promising NK and T cell-based therapies for BLCA.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1474652/fullbladder cancerprognosisCD56bright NKNK cellsTCGAanti-tumour immunity |
| spellingShingle | Md Abdullah Al Kamran Khan Alexander James Sedgwick Yuhan Sun Julian P. Vivian Julian P. Vivian Julian P. Vivian Alexandra J. Corbett Riccardo Dolcetti Riccardo Dolcetti Riccardo Dolcetti Theo Mantamadiotis Theo Mantamadiotis Stefano Mangiola Stefano Mangiola Stefano Mangiola Alexander David Barrow Transcriptional signature of CD56bright NK cells predicts favourable prognosis in bladder cancer Frontiers in Immunology bladder cancer prognosis CD56bright NK NK cells TCGA anti-tumour immunity |
| title | Transcriptional signature of CD56bright NK cells predicts favourable prognosis in bladder cancer |
| title_full | Transcriptional signature of CD56bright NK cells predicts favourable prognosis in bladder cancer |
| title_fullStr | Transcriptional signature of CD56bright NK cells predicts favourable prognosis in bladder cancer |
| title_full_unstemmed | Transcriptional signature of CD56bright NK cells predicts favourable prognosis in bladder cancer |
| title_short | Transcriptional signature of CD56bright NK cells predicts favourable prognosis in bladder cancer |
| title_sort | transcriptional signature of cd56bright nk cells predicts favourable prognosis in bladder cancer |
| topic | bladder cancer prognosis CD56bright NK NK cells TCGA anti-tumour immunity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1474652/full |
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