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Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma
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| Zeitschriftentitel: | Clinical Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , |
| In: | Clinical Cancer Research, 24, 2018, 22, S. 5685-5696 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
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| Schlagwörter: |
| author_facet |
Toker, Aras Nguyen, Linh T. Stone, Simone C. Yang, S.Y. Cindy Katz, Sarah Rachel Shaw, Patricia A. Clarke, Blaise A. Ghazarian, Danny Al-Habeeb, Ayman Easson, Alexandra Leong, Wey L. McCready, David R. Reedijk, Michael Guidos, Cynthia J. Pugh, Trevor J. Bernardini, Marcus Q. Ohashi, Pamela S. Toker, Aras Nguyen, Linh T. Stone, Simone C. Yang, S.Y. Cindy Katz, Sarah Rachel Shaw, Patricia A. Clarke, Blaise A. Ghazarian, Danny Al-Habeeb, Ayman Easson, Alexandra Leong, Wey L. McCready, David R. Reedijk, Michael Guidos, Cynthia J. Pugh, Trevor J. Bernardini, Marcus Q. Ohashi, Pamela S. |
|---|---|
| author |
Toker, Aras Nguyen, Linh T. Stone, Simone C. Yang, S.Y. Cindy Katz, Sarah Rachel Shaw, Patricia A. Clarke, Blaise A. Ghazarian, Danny Al-Habeeb, Ayman Easson, Alexandra Leong, Wey L. McCready, David R. Reedijk, Michael Guidos, Cynthia J. Pugh, Trevor J. Bernardini, Marcus Q. Ohashi, Pamela S. |
| spellingShingle |
Toker, Aras Nguyen, Linh T. Stone, Simone C. Yang, S.Y. Cindy Katz, Sarah Rachel Shaw, Patricia A. Clarke, Blaise A. Ghazarian, Danny Al-Habeeb, Ayman Easson, Alexandra Leong, Wey L. McCready, David R. Reedijk, Michael Guidos, Cynthia J. Pugh, Trevor J. Bernardini, Marcus Q. Ohashi, Pamela S. Clinical Cancer Research Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma Cancer Research Oncology |
| author_sort |
toker, aras |
| spelling |
Toker, Aras Nguyen, Linh T. Stone, Simone C. Yang, S.Y. Cindy Katz, Sarah Rachel Shaw, Patricia A. Clarke, Blaise A. Ghazarian, Danny Al-Habeeb, Ayman Easson, Alexandra Leong, Wey L. McCready, David R. Reedijk, Michael Guidos, Cynthia J. Pugh, Trevor J. Bernardini, Marcus Q. Ohashi, Pamela S. 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-18-0554 <jats:title>Abstract</jats:title> <jats:p>Purpose: Regulatory T (Treg) cells expressing the transcription factor FOXP3 are essential for the maintenance of immunologic self-tolerance but play a detrimental role in most cancers due to their ability to suppress antitumor immunity. The phenotype of human circulating Treg cells has been extensively studied, but less is known about tumor-infiltrating Treg cells. We studied the phenotype and function of tumor-infiltrating Treg cells in ovarian cancer and melanoma to identify potential Treg cell–associated molecules that can be targeted by tumor immunotherapies.</jats:p> <jats:p>Experimental Design: The phenotype of intratumoral and circulating Treg cells was analyzed by multicolor flow cytometry, mass cytometry, RNA-seq, and functional assays.</jats:p> <jats:p>Results: Treg cells isolated from ovarian tumors displayed a distinct cell surface phenotype with increased expression of a number of receptors associated with TCR engagement, including PD-1, 4-1BB, and ICOS. Higher PD-1 and 4-1BB expression was associated with increased responsiveness to further TCR stimulation and increased suppressive capacity, respectively. Transcriptomic and mass cytometry analyses revealed the presence of Treg cell subpopulations and further supported a highly activated state specifically in ovarian tumors. In comparison, Treg cells infiltrating melanomas displayed lower FOXP3, PD-1, 4-1BB, and ICOS expression and were less potent suppressors of CD8 T-cell proliferation.</jats:p> <jats:p>Conclusions: The highly activated phenotype of ovarian tumor-infiltrating Treg cells may be a key component of an immunosuppressive tumor microenvironment. Receptors that are expressed by tumor-infiltrating Treg cells could be exploited for the design of novel combination tumor immunotherapies. Clin Cancer Res; 24(22); 5685–96. ©2018 AACR.</jats:p> Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma Clinical Cancer Research |
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American Association for Cancer Research (AACR), 2018 |
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American Association for Cancer Research (AACR), 2018 |
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| title |
Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma |
| title_unstemmed |
Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma |
| title_full |
Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma |
| title_fullStr |
Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma |
| title_full_unstemmed |
Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma |
| title_short |
Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma |
| title_sort |
regulatory t cells in ovarian cancer are characterized by a highly activated phenotype distinct from that in melanoma |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/1078-0432.ccr-18-0554 |
| publishDate |
2018 |
| physical |
5685-5696 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Purpose: Regulatory T (Treg) cells expressing the transcription factor FOXP3 are essential for the maintenance of immunologic self-tolerance but play a detrimental role in most cancers due to their ability to suppress antitumor immunity. The phenotype of human circulating Treg cells has been extensively studied, but less is known about tumor-infiltrating Treg cells. We studied the phenotype and function of tumor-infiltrating Treg cells in ovarian cancer and melanoma to identify potential Treg cell–associated molecules that can be targeted by tumor immunotherapies.</jats:p>
<jats:p>Experimental Design: The phenotype of intratumoral and circulating Treg cells was analyzed by multicolor flow cytometry, mass cytometry, RNA-seq, and functional assays.</jats:p>
<jats:p>Results: Treg cells isolated from ovarian tumors displayed a distinct cell surface phenotype with increased expression of a number of receptors associated with TCR engagement, including PD-1, 4-1BB, and ICOS. Higher PD-1 and 4-1BB expression was associated with increased responsiveness to further TCR stimulation and increased suppressive capacity, respectively. Transcriptomic and mass cytometry analyses revealed the presence of Treg cell subpopulations and further supported a highly activated state specifically in ovarian tumors. In comparison, Treg cells infiltrating melanomas displayed lower FOXP3, PD-1, 4-1BB, and ICOS expression and were less potent suppressors of CD8 T-cell proliferation.</jats:p>
<jats:p>Conclusions: The highly activated phenotype of ovarian tumor-infiltrating Treg cells may be a key component of an immunosuppressive tumor microenvironment. Receptors that are expressed by tumor-infiltrating Treg cells could be exploited for the design of novel combination tumor immunotherapies. Clin Cancer Res; 24(22); 5685–96. ©2018 AACR.</jats:p> |
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| author | Toker, Aras, Nguyen, Linh T., Stone, Simone C., Yang, S.Y. Cindy, Katz, Sarah Rachel, Shaw, Patricia A., Clarke, Blaise A., Ghazarian, Danny, Al-Habeeb, Ayman, Easson, Alexandra, Leong, Wey L., McCready, David R., Reedijk, Michael, Guidos, Cynthia J., Pugh, Trevor J., Bernardini, Marcus Q., Ohashi, Pamela S. |
| author_facet | Toker, Aras, Nguyen, Linh T., Stone, Simone C., Yang, S.Y. Cindy, Katz, Sarah Rachel, Shaw, Patricia A., Clarke, Blaise A., Ghazarian, Danny, Al-Habeeb, Ayman, Easson, Alexandra, Leong, Wey L., McCready, David R., Reedijk, Michael, Guidos, Cynthia J., Pugh, Trevor J., Bernardini, Marcus Q., Ohashi, Pamela S., Toker, Aras, Nguyen, Linh T., Stone, Simone C., Yang, S.Y. Cindy, Katz, Sarah Rachel, Shaw, Patricia A., Clarke, Blaise A., Ghazarian, Danny, Al-Habeeb, Ayman, Easson, Alexandra, Leong, Wey L., McCready, David R., Reedijk, Michael, Guidos, Cynthia J., Pugh, Trevor J., Bernardini, Marcus Q., Ohashi, Pamela S. |
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| description | <jats:title>Abstract</jats:title> <jats:p>Purpose: Regulatory T (Treg) cells expressing the transcription factor FOXP3 are essential for the maintenance of immunologic self-tolerance but play a detrimental role in most cancers due to their ability to suppress antitumor immunity. The phenotype of human circulating Treg cells has been extensively studied, but less is known about tumor-infiltrating Treg cells. We studied the phenotype and function of tumor-infiltrating Treg cells in ovarian cancer and melanoma to identify potential Treg cell–associated molecules that can be targeted by tumor immunotherapies.</jats:p> <jats:p>Experimental Design: The phenotype of intratumoral and circulating Treg cells was analyzed by multicolor flow cytometry, mass cytometry, RNA-seq, and functional assays.</jats:p> <jats:p>Results: Treg cells isolated from ovarian tumors displayed a distinct cell surface phenotype with increased expression of a number of receptors associated with TCR engagement, including PD-1, 4-1BB, and ICOS. Higher PD-1 and 4-1BB expression was associated with increased responsiveness to further TCR stimulation and increased suppressive capacity, respectively. Transcriptomic and mass cytometry analyses revealed the presence of Treg cell subpopulations and further supported a highly activated state specifically in ovarian tumors. In comparison, Treg cells infiltrating melanomas displayed lower FOXP3, PD-1, 4-1BB, and ICOS expression and were less potent suppressors of CD8 T-cell proliferation.</jats:p> <jats:p>Conclusions: The highly activated phenotype of ovarian tumor-infiltrating Treg cells may be a key component of an immunosuppressive tumor microenvironment. Receptors that are expressed by tumor-infiltrating Treg cells could be exploited for the design of novel combination tumor immunotherapies. Clin Cancer Res; 24(22); 5685–96. ©2018 AACR.</jats:p> |
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| spelling | Toker, Aras Nguyen, Linh T. Stone, Simone C. Yang, S.Y. Cindy Katz, Sarah Rachel Shaw, Patricia A. Clarke, Blaise A. Ghazarian, Danny Al-Habeeb, Ayman Easson, Alexandra Leong, Wey L. McCready, David R. Reedijk, Michael Guidos, Cynthia J. Pugh, Trevor J. Bernardini, Marcus Q. Ohashi, Pamela S. 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-18-0554 <jats:title>Abstract</jats:title> <jats:p>Purpose: Regulatory T (Treg) cells expressing the transcription factor FOXP3 are essential for the maintenance of immunologic self-tolerance but play a detrimental role in most cancers due to their ability to suppress antitumor immunity. The phenotype of human circulating Treg cells has been extensively studied, but less is known about tumor-infiltrating Treg cells. We studied the phenotype and function of tumor-infiltrating Treg cells in ovarian cancer and melanoma to identify potential Treg cell–associated molecules that can be targeted by tumor immunotherapies.</jats:p> <jats:p>Experimental Design: The phenotype of intratumoral and circulating Treg cells was analyzed by multicolor flow cytometry, mass cytometry, RNA-seq, and functional assays.</jats:p> <jats:p>Results: Treg cells isolated from ovarian tumors displayed a distinct cell surface phenotype with increased expression of a number of receptors associated with TCR engagement, including PD-1, 4-1BB, and ICOS. Higher PD-1 and 4-1BB expression was associated with increased responsiveness to further TCR stimulation and increased suppressive capacity, respectively. Transcriptomic and mass cytometry analyses revealed the presence of Treg cell subpopulations and further supported a highly activated state specifically in ovarian tumors. In comparison, Treg cells infiltrating melanomas displayed lower FOXP3, PD-1, 4-1BB, and ICOS expression and were less potent suppressors of CD8 T-cell proliferation.</jats:p> <jats:p>Conclusions: The highly activated phenotype of ovarian tumor-infiltrating Treg cells may be a key component of an immunosuppressive tumor microenvironment. Receptors that are expressed by tumor-infiltrating Treg cells could be exploited for the design of novel combination tumor immunotherapies. Clin Cancer Res; 24(22); 5685–96. ©2018 AACR.</jats:p> Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma Clinical Cancer Research |
| spellingShingle | Toker, Aras, Nguyen, Linh T., Stone, Simone C., Yang, S.Y. Cindy, Katz, Sarah Rachel, Shaw, Patricia A., Clarke, Blaise A., Ghazarian, Danny, Al-Habeeb, Ayman, Easson, Alexandra, Leong, Wey L., McCready, David R., Reedijk, Michael, Guidos, Cynthia J., Pugh, Trevor J., Bernardini, Marcus Q., Ohashi, Pamela S., Clinical Cancer Research, Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma, Cancer Research, Oncology |
| title | Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma |
| title_full | Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma |
| title_fullStr | Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma |
| title_full_unstemmed | Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma |
| title_short | Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma |
| title_sort | regulatory t cells in ovarian cancer are characterized by a highly activated phenotype distinct from that in melanoma |
| title_unstemmed | Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/1078-0432.ccr-18-0554 |