CD70 in Thymic Squamous Cell Carcinoma: Potential Diagnostic Markers and Immunotherapeutic Targets
CD70 – a ligand protein of CD27 on lymphocytes – is expressed in a large spectrum of malignancies. It is an attractive target for antibody-based therapy and several clinical trials are currently being conducted. However, there is no evidence regarding the expression of CD70 and its relationship with...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-01-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.808396/full |
| _version_ | 1798025993095479296 |
|---|---|
| author | Jumpei Kashima Jumpei Kashima Tsunekazu Hishima Yusuke Okuma Hirotoshi Horio Masumi Ogawa Yukiko Hayashi Shin-ichiro Horiguchi Toru Motoi Tetsuo Ushiku Masashi Fukayama |
| author_facet | Jumpei Kashima Jumpei Kashima Tsunekazu Hishima Yusuke Okuma Hirotoshi Horio Masumi Ogawa Yukiko Hayashi Shin-ichiro Horiguchi Toru Motoi Tetsuo Ushiku Masashi Fukayama |
| author_sort | Jumpei Kashima |
| collection | DOAJ |
| description | CD70 – a ligand protein of CD27 on lymphocytes – is expressed in a large spectrum of malignancies. It is an attractive target for antibody-based therapy and several clinical trials are currently being conducted. However, there is no evidence regarding the expression of CD70 and its relationship with expression of programmed death ligand-1 (PD-L1) and CD27+ tumor-infiltrating lymphocytes (TIL) in formalin-fixed paraffin-embedded (FFPE) tissues of thymic tumors. FFPE tissues of thymic squamous cell carcinoma (TSCC) (operative specimens, n = 31; biopsy specimens, n = 11), thymoma (n = 60), thymic carcinoid (n = 3), and lung squamous cell carcinoma (LSCC) (n = 30) were analyzed immunohistochemically. Immunoreactivity for CD70 was semi-quantitatively scored according to the proportion of positive tumor cells. Moreover, the densities of CD27-positive intratumoral TIL (iTIL) and stromal TIL of TSCC were assessed and survival was compared. Most TSCC cases (87%; 27/31) were CD70-positive. In contrast, all thymoma and thymic carcinoid cases were CD70-negative. In LSCC cases, CD70-positivity was significantly lower than TSCC cases (20%; 6/30). Biopsy and resected specimens obtained from the same patients demonstrated a consistent staining pattern (6/6 patients). The proportion of CD70-positive TSCC was comparable with those of CD5 (87%) and CD117 (90%). Correlation between CD70 and PD-L1 expression score was observed. There was no significant difference in survival between the CD70-high and CD70-low expression groups. Meanwhile, patients with CD27-positive iTIL-high tumors exhibited better survival than those with iTIL-low tumors. This tendency was weaker in the CD70-high subset. CD70 immunohistochemistry is useful in diagnosing TSCC. CD70 may prevent anti-tumor immunity via CD27. Immunotherapy targeting the CD70–CD27 axis may be a promising option for the treatment of TSCC. |
| first_indexed | 2024-04-11T18:28:06Z |
| format | Article |
| id | doaj.art-c4b364a085804d6d96195d8f63b426a4 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T18:28:06Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-c4b364a085804d6d96195d8f63b426a42022-12-22T04:09:33ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-01-011110.3389/fonc.2021.808396808396CD70 in Thymic Squamous Cell Carcinoma: Potential Diagnostic Markers and Immunotherapeutic TargetsJumpei Kashima0Jumpei Kashima1Tsunekazu Hishima2Yusuke Okuma3Hirotoshi Horio4Masumi Ogawa5Yukiko Hayashi6Shin-ichiro Horiguchi7Toru Motoi8Tetsuo Ushiku9Masashi Fukayama10Department of Pathology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo, JapanDepartment of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Pathology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo, JapanDepartment of Thoracic Oncology and Respiratory Medicine, National Cancer Center, Tokyo, JapanDepartment of Thoracic Surgery, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo, JapanDepartment of Pathology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo, JapanDepartment of Pathology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo, JapanDepartment of Pathology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo, JapanDepartment of Pathology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo, JapanDepartment of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanCD70 – a ligand protein of CD27 on lymphocytes – is expressed in a large spectrum of malignancies. It is an attractive target for antibody-based therapy and several clinical trials are currently being conducted. However, there is no evidence regarding the expression of CD70 and its relationship with expression of programmed death ligand-1 (PD-L1) and CD27+ tumor-infiltrating lymphocytes (TIL) in formalin-fixed paraffin-embedded (FFPE) tissues of thymic tumors. FFPE tissues of thymic squamous cell carcinoma (TSCC) (operative specimens, n = 31; biopsy specimens, n = 11), thymoma (n = 60), thymic carcinoid (n = 3), and lung squamous cell carcinoma (LSCC) (n = 30) were analyzed immunohistochemically. Immunoreactivity for CD70 was semi-quantitatively scored according to the proportion of positive tumor cells. Moreover, the densities of CD27-positive intratumoral TIL (iTIL) and stromal TIL of TSCC were assessed and survival was compared. Most TSCC cases (87%; 27/31) were CD70-positive. In contrast, all thymoma and thymic carcinoid cases were CD70-negative. In LSCC cases, CD70-positivity was significantly lower than TSCC cases (20%; 6/30). Biopsy and resected specimens obtained from the same patients demonstrated a consistent staining pattern (6/6 patients). The proportion of CD70-positive TSCC was comparable with those of CD5 (87%) and CD117 (90%). Correlation between CD70 and PD-L1 expression score was observed. There was no significant difference in survival between the CD70-high and CD70-low expression groups. Meanwhile, patients with CD27-positive iTIL-high tumors exhibited better survival than those with iTIL-low tumors. This tendency was weaker in the CD70-high subset. CD70 immunohistochemistry is useful in diagnosing TSCC. CD70 may prevent anti-tumor immunity via CD27. Immunotherapy targeting the CD70–CD27 axis may be a promising option for the treatment of TSCC.https://www.frontiersin.org/articles/10.3389/fonc.2021.808396/fullthymic carcinomaCD70CD27immunohistochemistrytumor-infiltrating lymphocyte |
| spellingShingle | Jumpei Kashima Jumpei Kashima Tsunekazu Hishima Yusuke Okuma Hirotoshi Horio Masumi Ogawa Yukiko Hayashi Shin-ichiro Horiguchi Toru Motoi Tetsuo Ushiku Masashi Fukayama CD70 in Thymic Squamous Cell Carcinoma: Potential Diagnostic Markers and Immunotherapeutic Targets Frontiers in Oncology thymic carcinoma CD70 CD27 immunohistochemistry tumor-infiltrating lymphocyte |
| title | CD70 in Thymic Squamous Cell Carcinoma: Potential Diagnostic Markers and Immunotherapeutic Targets |
| title_full | CD70 in Thymic Squamous Cell Carcinoma: Potential Diagnostic Markers and Immunotherapeutic Targets |
| title_fullStr | CD70 in Thymic Squamous Cell Carcinoma: Potential Diagnostic Markers and Immunotherapeutic Targets |
| title_full_unstemmed | CD70 in Thymic Squamous Cell Carcinoma: Potential Diagnostic Markers and Immunotherapeutic Targets |
| title_short | CD70 in Thymic Squamous Cell Carcinoma: Potential Diagnostic Markers and Immunotherapeutic Targets |
| title_sort | cd70 in thymic squamous cell carcinoma potential diagnostic markers and immunotherapeutic targets |
| topic | thymic carcinoma CD70 CD27 immunohistochemistry tumor-infiltrating lymphocyte |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.808396/full |
| work_keys_str_mv | AT jumpeikashima cd70inthymicsquamouscellcarcinomapotentialdiagnosticmarkersandimmunotherapeutictargets AT jumpeikashima cd70inthymicsquamouscellcarcinomapotentialdiagnosticmarkersandimmunotherapeutictargets AT tsunekazuhishima cd70inthymicsquamouscellcarcinomapotentialdiagnosticmarkersandimmunotherapeutictargets AT yusukeokuma cd70inthymicsquamouscellcarcinomapotentialdiagnosticmarkersandimmunotherapeutictargets AT hirotoshihorio cd70inthymicsquamouscellcarcinomapotentialdiagnosticmarkersandimmunotherapeutictargets AT masumiogawa cd70inthymicsquamouscellcarcinomapotentialdiagnosticmarkersandimmunotherapeutictargets AT yukikohayashi cd70inthymicsquamouscellcarcinomapotentialdiagnosticmarkersandimmunotherapeutictargets AT shinichirohoriguchi cd70inthymicsquamouscellcarcinomapotentialdiagnosticmarkersandimmunotherapeutictargets AT torumotoi cd70inthymicsquamouscellcarcinomapotentialdiagnosticmarkersandimmunotherapeutictargets AT tetsuoushiku cd70inthymicsquamouscellcarcinomapotentialdiagnosticmarkersandimmunotherapeutictargets AT masashifukayama cd70inthymicsquamouscellcarcinomapotentialdiagnosticmarkersandimmunotherapeutictargets |