Single‐Cell Landscape Highlights Heterogenous Microenvironment, Novel Immune Reaction Patterns, Potential Biomarkers and Unique Therapeutic Strategies of Cervical Squamous Carcinoma, Human Papillomavirus‐Associated (HPVA) and Non‐HPVA Adenocarcinoma
Abstract Cervical adenocarcinomas (ADCs), including human papillomavirus (HPV)‐associated (HPVA) and non‐HPVA (NHPVA), though exhibiting a more malignant phenotype and poorer prognosis, are treated identically to squamous cell carcinoma (SCC). This clinical dilemma requires a deeper investigation in...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Junjun Qiu [verfasserIn] Xinyu Qu [verfasserIn] Yumeng Wang [verfasserIn] Chenyan Guo [verfasserIn] Bin Lv [verfasserIn] Qian Jiang [verfasserIn] Wentao Su [verfasserIn] Li Wang [verfasserIn] Keqin Hua [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2023 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
In: Advanced Science - Wiley, 2015, 10(2023), 10, Seite n/a-n/a |
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| Übergeordnetes Werk: |
volume:10 ; year:2023 ; number:10 ; pages:n/a-n/a |
| Links: |
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| DOI / URN: |
10.1002/advs.202204951 |
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| Katalog-ID: |
DOAJ089126963 |
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| 245 | 1 | 0 | |a Single‐Cell Landscape Highlights Heterogenous Microenvironment, Novel Immune Reaction Patterns, Potential Biomarkers and Unique Therapeutic Strategies of Cervical Squamous Carcinoma, Human Papillomavirus‐Associated (HPVA) and Non‐HPVA Adenocarcinoma |
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| 520 | |a Abstract Cervical adenocarcinomas (ADCs), including human papillomavirus (HPV)‐associated (HPVA) and non‐HPVA (NHPVA), though exhibiting a more malignant phenotype and poorer prognosis, are treated identically to squamous cell carcinoma (SCC). This clinical dilemma requires a deeper investigation into their differences. Herein a transcriptomic atlas of SCC, HPVA, and NHPVA‐ADC using single‐cell RNA (scRNA) and T‐cell receptor sequencing (TCR‐seq) is presented. Regarding structural cells, the malignancy origin of epithelial cells, angiogenic tip cells and two subtypes of fibroblasts is revealed. The promalignant properties of the structural cells using organoids are further confirmed. Regarding immune cells, myeloid cells with multiple functions other than antigen presentation and exhausted T lymphocytes contribute to immunosuppression. From the perspective of HPV infection, not only is HPV‐dependent and independent cervical cancer oncogenesis proposed but also three immune reaction patterns mediated by T cells (coordinated/inactive/imbalanced) are identified. Strikingly, diagnostic biomarkers to distinguish ADC from SCC are discovered and prognostic biomarkers with marker genes for malignant epithelial cells, tip cells, and SPP1/C1QC macrophages are generated. Importantly, the efficacy of anti‐CD96 and anti‐TIGIT, not inferior to anti‐PD1, in animal experiments is confirmed and targeted therapies specifically for HPV‐positive SCC, HPVA and NHPVA‐ADC, providing essential clues for further clinical trials, are proposed. | ||
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10.1002/advs.202204951 doi (DE-627)DOAJ089126963 (DE-599)DOAJ07f8f4046a7d459e8c331b3f044b88e9 DE-627 ger DE-627 rakwb eng Junjun Qiu verfasserin aut Single‐Cell Landscape Highlights Heterogenous Microenvironment, Novel Immune Reaction Patterns, Potential Biomarkers and Unique Therapeutic Strategies of Cervical Squamous Carcinoma, Human Papillomavirus‐Associated (HPVA) and Non‐HPVA Adenocarcinoma 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cervical adenocarcinomas (ADCs), including human papillomavirus (HPV)‐associated (HPVA) and non‐HPVA (NHPVA), though exhibiting a more malignant phenotype and poorer prognosis, are treated identically to squamous cell carcinoma (SCC). This clinical dilemma requires a deeper investigation into their differences. Herein a transcriptomic atlas of SCC, HPVA, and NHPVA‐ADC using single‐cell RNA (scRNA) and T‐cell receptor sequencing (TCR‐seq) is presented. Regarding structural cells, the malignancy origin of epithelial cells, angiogenic tip cells and two subtypes of fibroblasts is revealed. The promalignant properties of the structural cells using organoids are further confirmed. Regarding immune cells, myeloid cells with multiple functions other than antigen presentation and exhausted T lymphocytes contribute to immunosuppression. From the perspective of HPV infection, not only is HPV‐dependent and independent cervical cancer oncogenesis proposed but also three immune reaction patterns mediated by T cells (coordinated/inactive/imbalanced) are identified. Strikingly, diagnostic biomarkers to distinguish ADC from SCC are discovered and prognostic biomarkers with marker genes for malignant epithelial cells, tip cells, and SPP1/C1QC macrophages are generated. Importantly, the efficacy of anti‐CD96 and anti‐TIGIT, not inferior to anti‐PD1, in animal experiments is confirmed and targeted therapies specifically for HPV‐positive SCC, HPVA and NHPVA‐ADC, providing essential clues for further clinical trials, are proposed. cervical cancer HPV infection precise treatment scRNA‐seq TCR‐seq transcriptional heterogeneity Science Q Xinyu Qu verfasserin aut Yumeng Wang verfasserin aut Chenyan Guo verfasserin aut Bin Lv verfasserin aut Qian Jiang verfasserin aut Wentao Su verfasserin aut Li Wang verfasserin aut Keqin Hua verfasserin aut In Advanced Science Wiley, 2015 10(2023), 10, Seite n/a-n/a (DE-627)817357777 (DE-600)2808093-2 21983844 nnns volume:10 year:2023 number:10 pages:n/a-n/a https://doi.org/10.1002/advs.202204951 kostenfrei https://doaj.org/article/07f8f4046a7d459e8c331b3f044b88e9 kostenfrei https://doi.org/10.1002/advs.202204951 kostenfrei https://doaj.org/toc/2198-3844 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2023 10 n/a-n/a |
| spelling |
10.1002/advs.202204951 doi (DE-627)DOAJ089126963 (DE-599)DOAJ07f8f4046a7d459e8c331b3f044b88e9 DE-627 ger DE-627 rakwb eng Junjun Qiu verfasserin aut Single‐Cell Landscape Highlights Heterogenous Microenvironment, Novel Immune Reaction Patterns, Potential Biomarkers and Unique Therapeutic Strategies of Cervical Squamous Carcinoma, Human Papillomavirus‐Associated (HPVA) and Non‐HPVA Adenocarcinoma 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cervical adenocarcinomas (ADCs), including human papillomavirus (HPV)‐associated (HPVA) and non‐HPVA (NHPVA), though exhibiting a more malignant phenotype and poorer prognosis, are treated identically to squamous cell carcinoma (SCC). This clinical dilemma requires a deeper investigation into their differences. Herein a transcriptomic atlas of SCC, HPVA, and NHPVA‐ADC using single‐cell RNA (scRNA) and T‐cell receptor sequencing (TCR‐seq) is presented. Regarding structural cells, the malignancy origin of epithelial cells, angiogenic tip cells and two subtypes of fibroblasts is revealed. The promalignant properties of the structural cells using organoids are further confirmed. Regarding immune cells, myeloid cells with multiple functions other than antigen presentation and exhausted T lymphocytes contribute to immunosuppression. From the perspective of HPV infection, not only is HPV‐dependent and independent cervical cancer oncogenesis proposed but also three immune reaction patterns mediated by T cells (coordinated/inactive/imbalanced) are identified. Strikingly, diagnostic biomarkers to distinguish ADC from SCC are discovered and prognostic biomarkers with marker genes for malignant epithelial cells, tip cells, and SPP1/C1QC macrophages are generated. Importantly, the efficacy of anti‐CD96 and anti‐TIGIT, not inferior to anti‐PD1, in animal experiments is confirmed and targeted therapies specifically for HPV‐positive SCC, HPVA and NHPVA‐ADC, providing essential clues for further clinical trials, are proposed. cervical cancer HPV infection precise treatment scRNA‐seq TCR‐seq transcriptional heterogeneity Science Q Xinyu Qu verfasserin aut Yumeng Wang verfasserin aut Chenyan Guo verfasserin aut Bin Lv verfasserin aut Qian Jiang verfasserin aut Wentao Su verfasserin aut Li Wang verfasserin aut Keqin Hua verfasserin aut In Advanced Science Wiley, 2015 10(2023), 10, Seite n/a-n/a (DE-627)817357777 (DE-600)2808093-2 21983844 nnns volume:10 year:2023 number:10 pages:n/a-n/a https://doi.org/10.1002/advs.202204951 kostenfrei https://doaj.org/article/07f8f4046a7d459e8c331b3f044b88e9 kostenfrei https://doi.org/10.1002/advs.202204951 kostenfrei https://doaj.org/toc/2198-3844 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2023 10 n/a-n/a |
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10.1002/advs.202204951 doi (DE-627)DOAJ089126963 (DE-599)DOAJ07f8f4046a7d459e8c331b3f044b88e9 DE-627 ger DE-627 rakwb eng Junjun Qiu verfasserin aut Single‐Cell Landscape Highlights Heterogenous Microenvironment, Novel Immune Reaction Patterns, Potential Biomarkers and Unique Therapeutic Strategies of Cervical Squamous Carcinoma, Human Papillomavirus‐Associated (HPVA) and Non‐HPVA Adenocarcinoma 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cervical adenocarcinomas (ADCs), including human papillomavirus (HPV)‐associated (HPVA) and non‐HPVA (NHPVA), though exhibiting a more malignant phenotype and poorer prognosis, are treated identically to squamous cell carcinoma (SCC). This clinical dilemma requires a deeper investigation into their differences. Herein a transcriptomic atlas of SCC, HPVA, and NHPVA‐ADC using single‐cell RNA (scRNA) and T‐cell receptor sequencing (TCR‐seq) is presented. Regarding structural cells, the malignancy origin of epithelial cells, angiogenic tip cells and two subtypes of fibroblasts is revealed. The promalignant properties of the structural cells using organoids are further confirmed. Regarding immune cells, myeloid cells with multiple functions other than antigen presentation and exhausted T lymphocytes contribute to immunosuppression. From the perspective of HPV infection, not only is HPV‐dependent and independent cervical cancer oncogenesis proposed but also three immune reaction patterns mediated by T cells (coordinated/inactive/imbalanced) are identified. Strikingly, diagnostic biomarkers to distinguish ADC from SCC are discovered and prognostic biomarkers with marker genes for malignant epithelial cells, tip cells, and SPP1/C1QC macrophages are generated. Importantly, the efficacy of anti‐CD96 and anti‐TIGIT, not inferior to anti‐PD1, in animal experiments is confirmed and targeted therapies specifically for HPV‐positive SCC, HPVA and NHPVA‐ADC, providing essential clues for further clinical trials, are proposed. cervical cancer HPV infection precise treatment scRNA‐seq TCR‐seq transcriptional heterogeneity Science Q Xinyu Qu verfasserin aut Yumeng Wang verfasserin aut Chenyan Guo verfasserin aut Bin Lv verfasserin aut Qian Jiang verfasserin aut Wentao Su verfasserin aut Li Wang verfasserin aut Keqin Hua verfasserin aut In Advanced Science Wiley, 2015 10(2023), 10, Seite n/a-n/a (DE-627)817357777 (DE-600)2808093-2 21983844 nnns volume:10 year:2023 number:10 pages:n/a-n/a https://doi.org/10.1002/advs.202204951 kostenfrei https://doaj.org/article/07f8f4046a7d459e8c331b3f044b88e9 kostenfrei https://doi.org/10.1002/advs.202204951 kostenfrei https://doaj.org/toc/2198-3844 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2023 10 n/a-n/a |
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10.1002/advs.202204951 doi (DE-627)DOAJ089126963 (DE-599)DOAJ07f8f4046a7d459e8c331b3f044b88e9 DE-627 ger DE-627 rakwb eng Junjun Qiu verfasserin aut Single‐Cell Landscape Highlights Heterogenous Microenvironment, Novel Immune Reaction Patterns, Potential Biomarkers and Unique Therapeutic Strategies of Cervical Squamous Carcinoma, Human Papillomavirus‐Associated (HPVA) and Non‐HPVA Adenocarcinoma 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cervical adenocarcinomas (ADCs), including human papillomavirus (HPV)‐associated (HPVA) and non‐HPVA (NHPVA), though exhibiting a more malignant phenotype and poorer prognosis, are treated identically to squamous cell carcinoma (SCC). This clinical dilemma requires a deeper investigation into their differences. Herein a transcriptomic atlas of SCC, HPVA, and NHPVA‐ADC using single‐cell RNA (scRNA) and T‐cell receptor sequencing (TCR‐seq) is presented. Regarding structural cells, the malignancy origin of epithelial cells, angiogenic tip cells and two subtypes of fibroblasts is revealed. The promalignant properties of the structural cells using organoids are further confirmed. Regarding immune cells, myeloid cells with multiple functions other than antigen presentation and exhausted T lymphocytes contribute to immunosuppression. From the perspective of HPV infection, not only is HPV‐dependent and independent cervical cancer oncogenesis proposed but also three immune reaction patterns mediated by T cells (coordinated/inactive/imbalanced) are identified. Strikingly, diagnostic biomarkers to distinguish ADC from SCC are discovered and prognostic biomarkers with marker genes for malignant epithelial cells, tip cells, and SPP1/C1QC macrophages are generated. Importantly, the efficacy of anti‐CD96 and anti‐TIGIT, not inferior to anti‐PD1, in animal experiments is confirmed and targeted therapies specifically for HPV‐positive SCC, HPVA and NHPVA‐ADC, providing essential clues for further clinical trials, are proposed. cervical cancer HPV infection precise treatment scRNA‐seq TCR‐seq transcriptional heterogeneity Science Q Xinyu Qu verfasserin aut Yumeng Wang verfasserin aut Chenyan Guo verfasserin aut Bin Lv verfasserin aut Qian Jiang verfasserin aut Wentao Su verfasserin aut Li Wang verfasserin aut Keqin Hua verfasserin aut In Advanced Science Wiley, 2015 10(2023), 10, Seite n/a-n/a (DE-627)817357777 (DE-600)2808093-2 21983844 nnns volume:10 year:2023 number:10 pages:n/a-n/a https://doi.org/10.1002/advs.202204951 kostenfrei https://doaj.org/article/07f8f4046a7d459e8c331b3f044b88e9 kostenfrei https://doi.org/10.1002/advs.202204951 kostenfrei https://doaj.org/toc/2198-3844 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2023 10 n/a-n/a |
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Junjun Qiu misc cervical cancer misc HPV infection misc precise treatment misc scRNA‐seq misc TCR‐seq misc transcriptional heterogeneity misc Science misc Q Single‐Cell Landscape Highlights Heterogenous Microenvironment, Novel Immune Reaction Patterns, Potential Biomarkers and Unique Therapeutic Strategies of Cervical Squamous Carcinoma, Human Papillomavirus‐Associated (HPVA) and Non‐HPVA Adenocarcinoma |
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Single‐Cell Landscape Highlights Heterogenous Microenvironment, Novel Immune Reaction Patterns, Potential Biomarkers and Unique Therapeutic Strategies of Cervical Squamous Carcinoma, Human Papillomavirus‐Associated (HPVA) and Non‐HPVA Adenocarcinoma cervical cancer HPV infection precise treatment scRNA‐seq TCR‐seq transcriptional heterogeneity |
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Single‐Cell Landscape Highlights Heterogenous Microenvironment, Novel Immune Reaction Patterns, Potential Biomarkers and Unique Therapeutic Strategies of Cervical Squamous Carcinoma, Human Papillomavirus‐Associated (HPVA) and Non‐HPVA Adenocarcinoma |
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Single‐Cell Landscape Highlights Heterogenous Microenvironment, Novel Immune Reaction Patterns, Potential Biomarkers and Unique Therapeutic Strategies of Cervical Squamous Carcinoma, Human Papillomavirus‐Associated (HPVA) and Non‐HPVA Adenocarcinoma |
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single‐cell landscape highlights heterogenous microenvironment, novel immune reaction patterns, potential biomarkers and unique therapeutic strategies of cervical squamous carcinoma, human papillomavirus‐associated (hpva) and non‐hpva adenocarcinoma |
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Single‐Cell Landscape Highlights Heterogenous Microenvironment, Novel Immune Reaction Patterns, Potential Biomarkers and Unique Therapeutic Strategies of Cervical Squamous Carcinoma, Human Papillomavirus‐Associated (HPVA) and Non‐HPVA Adenocarcinoma |
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Abstract Cervical adenocarcinomas (ADCs), including human papillomavirus (HPV)‐associated (HPVA) and non‐HPVA (NHPVA), though exhibiting a more malignant phenotype and poorer prognosis, are treated identically to squamous cell carcinoma (SCC). This clinical dilemma requires a deeper investigation into their differences. Herein a transcriptomic atlas of SCC, HPVA, and NHPVA‐ADC using single‐cell RNA (scRNA) and T‐cell receptor sequencing (TCR‐seq) is presented. Regarding structural cells, the malignancy origin of epithelial cells, angiogenic tip cells and two subtypes of fibroblasts is revealed. The promalignant properties of the structural cells using organoids are further confirmed. Regarding immune cells, myeloid cells with multiple functions other than antigen presentation and exhausted T lymphocytes contribute to immunosuppression. From the perspective of HPV infection, not only is HPV‐dependent and independent cervical cancer oncogenesis proposed but also three immune reaction patterns mediated by T cells (coordinated/inactive/imbalanced) are identified. Strikingly, diagnostic biomarkers to distinguish ADC from SCC are discovered and prognostic biomarkers with marker genes for malignant epithelial cells, tip cells, and SPP1/C1QC macrophages are generated. Importantly, the efficacy of anti‐CD96 and anti‐TIGIT, not inferior to anti‐PD1, in animal experiments is confirmed and targeted therapies specifically for HPV‐positive SCC, HPVA and NHPVA‐ADC, providing essential clues for further clinical trials, are proposed. |
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Abstract Cervical adenocarcinomas (ADCs), including human papillomavirus (HPV)‐associated (HPVA) and non‐HPVA (NHPVA), though exhibiting a more malignant phenotype and poorer prognosis, are treated identically to squamous cell carcinoma (SCC). This clinical dilemma requires a deeper investigation into their differences. Herein a transcriptomic atlas of SCC, HPVA, and NHPVA‐ADC using single‐cell RNA (scRNA) and T‐cell receptor sequencing (TCR‐seq) is presented. Regarding structural cells, the malignancy origin of epithelial cells, angiogenic tip cells and two subtypes of fibroblasts is revealed. The promalignant properties of the structural cells using organoids are further confirmed. Regarding immune cells, myeloid cells with multiple functions other than antigen presentation and exhausted T lymphocytes contribute to immunosuppression. From the perspective of HPV infection, not only is HPV‐dependent and independent cervical cancer oncogenesis proposed but also three immune reaction patterns mediated by T cells (coordinated/inactive/imbalanced) are identified. Strikingly, diagnostic biomarkers to distinguish ADC from SCC are discovered and prognostic biomarkers with marker genes for malignant epithelial cells, tip cells, and SPP1/C1QC macrophages are generated. Importantly, the efficacy of anti‐CD96 and anti‐TIGIT, not inferior to anti‐PD1, in animal experiments is confirmed and targeted therapies specifically for HPV‐positive SCC, HPVA and NHPVA‐ADC, providing essential clues for further clinical trials, are proposed. |
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Abstract Cervical adenocarcinomas (ADCs), including human papillomavirus (HPV)‐associated (HPVA) and non‐HPVA (NHPVA), though exhibiting a more malignant phenotype and poorer prognosis, are treated identically to squamous cell carcinoma (SCC). This clinical dilemma requires a deeper investigation into their differences. Herein a transcriptomic atlas of SCC, HPVA, and NHPVA‐ADC using single‐cell RNA (scRNA) and T‐cell receptor sequencing (TCR‐seq) is presented. Regarding structural cells, the malignancy origin of epithelial cells, angiogenic tip cells and two subtypes of fibroblasts is revealed. The promalignant properties of the structural cells using organoids are further confirmed. Regarding immune cells, myeloid cells with multiple functions other than antigen presentation and exhausted T lymphocytes contribute to immunosuppression. From the perspective of HPV infection, not only is HPV‐dependent and independent cervical cancer oncogenesis proposed but also three immune reaction patterns mediated by T cells (coordinated/inactive/imbalanced) are identified. Strikingly, diagnostic biomarkers to distinguish ADC from SCC are discovered and prognostic biomarkers with marker genes for malignant epithelial cells, tip cells, and SPP1/C1QC macrophages are generated. Importantly, the efficacy of anti‐CD96 and anti‐TIGIT, not inferior to anti‐PD1, in animal experiments is confirmed and targeted therapies specifically for HPV‐positive SCC, HPVA and NHPVA‐ADC, providing essential clues for further clinical trials, are proposed. |
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