Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy
Extramammary Paget disease (EMPD) is a locally aggressive cutaneous malignancy that usually arises in anogenital or axillary skin. Immune checkpoint inhibitors targeting programmed cell death receptor (PD-1) and/or its ligand (PD-L1) are approved for the treatment of several types of cancer, and res...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/6/754 |
| _version_ | 1797714371373170688 |
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| author | Shakuntala H. Mauzo Michael T. Tetzlaff Denái R. Milton Alan E. Siroy Priyadharsini Nagarajan Carlos A. Torres-Cabala Doina Ivan Jonathan L. Curry Courtney W. Hudgens Jennifer A. Wargo Aysegul A. Sahin Curtis A. Pettaway Victor G. Prieto Phyu P. Aung |
| author_facet | Shakuntala H. Mauzo Michael T. Tetzlaff Denái R. Milton Alan E. Siroy Priyadharsini Nagarajan Carlos A. Torres-Cabala Doina Ivan Jonathan L. Curry Courtney W. Hudgens Jennifer A. Wargo Aysegul A. Sahin Curtis A. Pettaway Victor G. Prieto Phyu P. Aung |
| author_sort | Shakuntala H. Mauzo |
| collection | DOAJ |
| description | Extramammary Paget disease (EMPD) is a locally aggressive cutaneous malignancy that usually arises in anogenital or axillary skin. Immune checkpoint inhibitors targeting programmed cell death receptor (PD-1) and/or its ligand (PD-L1) are approved for the treatment of several types of cancer, and response to these generally correlates with increased PD-L1 expression by tumor cells. The expression of PD-L1 and composition and density of the tumor-associated immune infiltrate in EMPD have been little studied. To determine whether EMPD might be amenable to immune checkpoint blockade, we analyzed the expression of PD-1 and PD-L1 and the composition and density of the tumor-associated immune infiltrate in EMPD and evaluated associations between biomarker expression and clinicopathologic parameters. Twenty-one EMPD tumors were evaluated for tumor cell PD-L1 expression and for relative expression and distribution of CD3, CD8, PD-1, and PD-L1 in the tumor-associated immune infiltrate by using a combination of visual and image analysis (Aperio ImageScope). In addition, PD-L1 expression was assessed in 10 cases of mammary Paget disease (MPD). In EMPD cases, PD-L1 was expressed by tumor cells (3/21; 14%) and the tumor-associated immune infiltrate (15/21; 71%), and PD-1 was expressed by the tumor-associated immune infiltrate in all cases analyzed (18/18). However, PD-L1 expression by EMPD tumor cells did not correlate with the density of CD3-, CD8-, or PD-1-positive cells in the tumor-associated immune infiltrate or other clinicopathologic parameters. Furthermore, the density of CD3, CD8, PD-1, and PD-L1 in the tumor-associated immune infiltrate did not correlate with any clinicopathologic parameters evaluated with the exception that CD3 positive values were significantly higher in patients who were still alive (median, 1310 cells/mm<sup>2</sup>; range, 543−2115;) than in those who died (median, 611 cells/mm<sup>2</sup>; range, 481−908; <i>p</i> = 0.049). In all MPD cases, PD-L1 was absent in tumor cells but present in the tumor-associated immune infiltrate, and PD-L1 expression in lymphocytes was lower in patients with HER2/neu-positive than in those with HER2/neu-negative disease (<i>p</i> = 0.07). Our findings raise the possibility of therapeutic targeting of the PD-1/PD-L1 axis in EMPD. |
| first_indexed | 2024-03-12T07:50:55Z |
| format | Article |
| id | doaj.art-8a11b7535a764ba98d2a2a7e22082ace |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:50:55Z |
| publishDate | 2019-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-8a11b7535a764ba98d2a2a7e22082ace2023-09-02T20:36:26ZengMDPI AGCancers2072-66942019-05-0111675410.3390/cancers11060754cancers11060754Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted TherapyShakuntala H. Mauzo0Michael T. Tetzlaff1Denái R. Milton2Alan E. Siroy3Priyadharsini Nagarajan4Carlos A. Torres-Cabala5Doina Ivan6Jonathan L. Curry7Courtney W. Hudgens8Jennifer A. Wargo9Aysegul A. Sahin10Curtis A. Pettaway11Victor G. Prieto12Phyu P. Aung13Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAExtramammary Paget disease (EMPD) is a locally aggressive cutaneous malignancy that usually arises in anogenital or axillary skin. Immune checkpoint inhibitors targeting programmed cell death receptor (PD-1) and/or its ligand (PD-L1) are approved for the treatment of several types of cancer, and response to these generally correlates with increased PD-L1 expression by tumor cells. The expression of PD-L1 and composition and density of the tumor-associated immune infiltrate in EMPD have been little studied. To determine whether EMPD might be amenable to immune checkpoint blockade, we analyzed the expression of PD-1 and PD-L1 and the composition and density of the tumor-associated immune infiltrate in EMPD and evaluated associations between biomarker expression and clinicopathologic parameters. Twenty-one EMPD tumors were evaluated for tumor cell PD-L1 expression and for relative expression and distribution of CD3, CD8, PD-1, and PD-L1 in the tumor-associated immune infiltrate by using a combination of visual and image analysis (Aperio ImageScope). In addition, PD-L1 expression was assessed in 10 cases of mammary Paget disease (MPD). In EMPD cases, PD-L1 was expressed by tumor cells (3/21; 14%) and the tumor-associated immune infiltrate (15/21; 71%), and PD-1 was expressed by the tumor-associated immune infiltrate in all cases analyzed (18/18). However, PD-L1 expression by EMPD tumor cells did not correlate with the density of CD3-, CD8-, or PD-1-positive cells in the tumor-associated immune infiltrate or other clinicopathologic parameters. Furthermore, the density of CD3, CD8, PD-1, and PD-L1 in the tumor-associated immune infiltrate did not correlate with any clinicopathologic parameters evaluated with the exception that CD3 positive values were significantly higher in patients who were still alive (median, 1310 cells/mm<sup>2</sup>; range, 543−2115;) than in those who died (median, 611 cells/mm<sup>2</sup>; range, 481−908; <i>p</i> = 0.049). In all MPD cases, PD-L1 was absent in tumor cells but present in the tumor-associated immune infiltrate, and PD-L1 expression in lymphocytes was lower in patients with HER2/neu-positive than in those with HER2/neu-negative disease (<i>p</i> = 0.07). Our findings raise the possibility of therapeutic targeting of the PD-1/PD-L1 axis in EMPD.https://www.mdpi.com/2072-6694/11/6/754extramammary Paget diseasemammary Paget diseasePD-1PD-L1immune infiltrate |
| spellingShingle | Shakuntala H. Mauzo Michael T. Tetzlaff Denái R. Milton Alan E. Siroy Priyadharsini Nagarajan Carlos A. Torres-Cabala Doina Ivan Jonathan L. Curry Courtney W. Hudgens Jennifer A. Wargo Aysegul A. Sahin Curtis A. Pettaway Victor G. Prieto Phyu P. Aung Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy Cancers extramammary Paget disease mammary Paget disease PD-1 PD-L1 immune infiltrate |
| title | Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy |
| title_full | Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy |
| title_fullStr | Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy |
| title_full_unstemmed | Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy |
| title_short | Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy |
| title_sort | expression of pd 1 and pd l1 in extramammary paget disease implications for immune targeted therapy |
| topic | extramammary Paget disease mammary Paget disease PD-1 PD-L1 immune infiltrate |
| url | https://www.mdpi.com/2072-6694/11/6/754 |
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