RETRACTED: Tumor Microenvironment in Oral Cancer Following Neoadjuvant Pembrolizumab: Preliminary Analysis of the Histopathologic Findings
Background: The tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC) is associated with immune suppression, one of the pathways being the programmed death receptor 1 (PD-1) and its ligands (PD-L1/PD-L2). Checkpoint inhibitors of PD-1/PD-L1, like pembrolizumab, have been recently appro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Oral Health |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/froh.2021.653104/full |
| _version_ | 1827297766376734720 |
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| author | Alex Dobriyan Iris Gluck Iris Gluck Eran Alon Eran Alon Iris Barshack Iris Barshack Ran Yahalom Marilena Vered Marilena Vered |
| author_facet | Alex Dobriyan Iris Gluck Iris Gluck Eran Alon Eran Alon Iris Barshack Iris Barshack Ran Yahalom Marilena Vered Marilena Vered |
| author_sort | Alex Dobriyan |
| collection | DOAJ |
| description | Background: The tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC) is associated with immune suppression, one of the pathways being the programmed death receptor 1 (PD-1) and its ligands (PD-L1/PD-L2). Checkpoint inhibitors of PD-1/PD-L1, like pembrolizumab, have been recently approved for treatment of OSCC. We described the histologic findings in OSCC following neoadjuvant pembrolizumab, including identification of immune-related cell populations and cancer-associated fibroblasts (CAFs).Materials and Methods: Patients with OSCC clinical stages 3 and 4 and a combined PD-L1 score >1 were randomized either to the standard oncologic protocol or to the pembrolizumab arm of MK-3475-689 study for Head and Neck, Lip, and Oral Cavity. The latter were given two standard doses of 200 mg of pembrolizumab, 3 weeks apart, and then underwent surgical oncologic procedure according to the initial stage. Sections from the resection specimens were analyzed for pathological response to pembrolizumab. Various populations of immune-related cells within the tumor microenvironment were characterized by immunohistochemistry, as were the CAFs.Results: Three patients who were randomized to the pembrolizumab study were described. One patient presented with a tongue SCC, the other two had SCC of the mandibular ridge with bony involvement. Only the patient with tongue SCC showed clinical complete response. Microscopically, the tumor was replaced by a granulomatous type of inflammation. Immunohistochemical stains revealed massive T cell rich (CD3+) infiltrate, with approximately equal amounts of CD4+ and CD8+ cells, numerous macrophages of CD68+ and CD163+ phenotypes; no CAFs were identified. The other two patients were regarded as non-responders as at least 50% of the tumor was viable. The tumor microenvironment of these tumors was generally associated with a lesser extent of inflammatory response compared to the tongue tumor, a variable CD4+/CD8+ ratio and presence of CAFs. Neither T regulatory cells (FOXP3+) nor natural killer cells (CD56+, CD57+) were identified in any of the cases.Conclusion: We showed that characterizing the specific populations of immune-related cells and CAFs after treatment with pembrolizumab, may add to our understanding of the tumor-TME interactions in this setting. These findings should be investigated in future studies on a larger number of patients. |
| first_indexed | 2024-04-24T15:02:03Z |
| format | Article |
| id | doaj.art-6ba9ee45480c46a6aa46ba57a2dd149d |
| institution | Directory Open Access Journal |
| issn | 2673-4842 |
| language | English |
| last_indexed | 2024-04-24T15:02:03Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oral Health |
| spelling | doaj.art-6ba9ee45480c46a6aa46ba57a2dd149d2024-04-02T15:10:36ZengFrontiers Media S.A.Frontiers in Oral Health2673-48422021-04-01210.3389/froh.2021.653104653104RETRACTED: Tumor Microenvironment in Oral Cancer Following Neoadjuvant Pembrolizumab: Preliminary Analysis of the Histopathologic FindingsAlex Dobriyan0Iris Gluck1Iris Gluck2Eran Alon3Eran Alon4Iris Barshack5Iris Barshack6Ran Yahalom7Marilena Vered8Marilena Vered9Department of Oral and Maxillofacial Surgery, The Chaim Sheba Medical Center, Tel Hashomer, IsraelHead and Neck Cancer Unit, The Chaim Sheba Medical Center, Institute of Oncology, Tel Hashomer, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Otolaryngology—Head and Neck Surgery, The Chaim Sheba Medical Center, Tel Hashomer, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelThe Chaim Sheba Medical Center, Institute of Pathology, Tel Hashomer, IsraelDepartment of Oral and Maxillofacial Surgery, The Chaim Sheba Medical Center, Tel Hashomer, IsraelThe Chaim Sheba Medical Center, Institute of Pathology, Tel Hashomer, IsraelDepartment of Oral Pathology, Oral Medicine and Maxillofacial Imaging, School of Dentistry, Tel Aviv University, Tel Aviv, IsraelBackground: The tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC) is associated with immune suppression, one of the pathways being the programmed death receptor 1 (PD-1) and its ligands (PD-L1/PD-L2). Checkpoint inhibitors of PD-1/PD-L1, like pembrolizumab, have been recently approved for treatment of OSCC. We described the histologic findings in OSCC following neoadjuvant pembrolizumab, including identification of immune-related cell populations and cancer-associated fibroblasts (CAFs).Materials and Methods: Patients with OSCC clinical stages 3 and 4 and a combined PD-L1 score >1 were randomized either to the standard oncologic protocol or to the pembrolizumab arm of MK-3475-689 study for Head and Neck, Lip, and Oral Cavity. The latter were given two standard doses of 200 mg of pembrolizumab, 3 weeks apart, and then underwent surgical oncologic procedure according to the initial stage. Sections from the resection specimens were analyzed for pathological response to pembrolizumab. Various populations of immune-related cells within the tumor microenvironment were characterized by immunohistochemistry, as were the CAFs.Results: Three patients who were randomized to the pembrolizumab study were described. One patient presented with a tongue SCC, the other two had SCC of the mandibular ridge with bony involvement. Only the patient with tongue SCC showed clinical complete response. Microscopically, the tumor was replaced by a granulomatous type of inflammation. Immunohistochemical stains revealed massive T cell rich (CD3+) infiltrate, with approximately equal amounts of CD4+ and CD8+ cells, numerous macrophages of CD68+ and CD163+ phenotypes; no CAFs were identified. The other two patients were regarded as non-responders as at least 50% of the tumor was viable. The tumor microenvironment of these tumors was generally associated with a lesser extent of inflammatory response compared to the tongue tumor, a variable CD4+/CD8+ ratio and presence of CAFs. Neither T regulatory cells (FOXP3+) nor natural killer cells (CD56+, CD57+) were identified in any of the cases.Conclusion: We showed that characterizing the specific populations of immune-related cells and CAFs after treatment with pembrolizumab, may add to our understanding of the tumor-TME interactions in this setting. These findings should be investigated in future studies on a larger number of patients.https://www.frontiersin.org/articles/10.3389/froh.2021.653104/fulloral squamous cell carcinomapembrolizumabtumor microenviromentimmune reactioncancer-associate fibroblasts |
| spellingShingle | Alex Dobriyan Iris Gluck Iris Gluck Eran Alon Eran Alon Iris Barshack Iris Barshack Ran Yahalom Marilena Vered Marilena Vered RETRACTED: Tumor Microenvironment in Oral Cancer Following Neoadjuvant Pembrolizumab: Preliminary Analysis of the Histopathologic Findings Frontiers in Oral Health oral squamous cell carcinoma pembrolizumab tumor microenviroment immune reaction cancer-associate fibroblasts |
| title | RETRACTED: Tumor Microenvironment in Oral Cancer Following Neoadjuvant Pembrolizumab: Preliminary Analysis of the Histopathologic Findings |
| title_full | RETRACTED: Tumor Microenvironment in Oral Cancer Following Neoadjuvant Pembrolizumab: Preliminary Analysis of the Histopathologic Findings |
| title_fullStr | RETRACTED: Tumor Microenvironment in Oral Cancer Following Neoadjuvant Pembrolizumab: Preliminary Analysis of the Histopathologic Findings |
| title_full_unstemmed | RETRACTED: Tumor Microenvironment in Oral Cancer Following Neoadjuvant Pembrolizumab: Preliminary Analysis of the Histopathologic Findings |
| title_short | RETRACTED: Tumor Microenvironment in Oral Cancer Following Neoadjuvant Pembrolizumab: Preliminary Analysis of the Histopathologic Findings |
| title_sort | retracted tumor microenvironment in oral cancer following neoadjuvant pembrolizumab preliminary analysis of the histopathologic findings |
| topic | oral squamous cell carcinoma pembrolizumab tumor microenviroment immune reaction cancer-associate fibroblasts |
| url | https://www.frontiersin.org/articles/10.3389/froh.2021.653104/full |
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