The Tumor Microenvironment in SCC: Mechanisms and Therapeutic Opportunities
Squamous cell carcinoma (SCC) is the second most common skin cancer worldwide and, despite the relatively easy visualization of the tumor in the clinic, a sizeable number of SCC patients are diagnosed at advanced stages with local invasion and distant metastatic lesions. In the last decade, immunoth...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-02-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.636544/full |
| _version_ | 1818359924551319552 |
|---|---|
| author | Nádia Ghinelli Amôr Paulo Sérgio da Silva Santos Ana Paula Campanelli |
| author_facet | Nádia Ghinelli Amôr Paulo Sérgio da Silva Santos Ana Paula Campanelli |
| author_sort | Nádia Ghinelli Amôr |
| collection | DOAJ |
| description | Squamous cell carcinoma (SCC) is the second most common skin cancer worldwide and, despite the relatively easy visualization of the tumor in the clinic, a sizeable number of SCC patients are diagnosed at advanced stages with local invasion and distant metastatic lesions. In the last decade, immunotherapy has emerged as the fourth pillar in cancer therapy via the targeting of immune checkpoint molecules such as programmed cell-death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). FDA-approved monoclonal antibodies directed against these immune targets have provide survival benefit in a growing list of cancer types. Currently, there are two immunotherapy drugs available for cutaneous SCC: cemiplimab and pembrolizumab; both monoclonal antibodies (mAb) that block PD-1 thereby promoting T-cell activation and/or function. However, the success rate of these checkpoint inhibitors currently remains around 50%, which means that half of the patients with advanced SCC experience no benefit from this treatment. This review will highlight the mechanisms by which the immune checkpoint molecules regulate the tumor microenvironment (TME), as well as the ongoing clinical trials that are employing single or combinatory therapeutic approaches for SCC immunotherapy. We also discuss the regulation of additional pathways that might promote superior therapeutic efficacy, and consequently provide increased survival for those patients that do not benefit from the current checkpoint inhibitor therapies. |
| first_indexed | 2024-12-13T20:52:38Z |
| format | Article |
| id | doaj.art-85211f07060c477a9f883b0d919b8423 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-13T20:52:38Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-85211f07060c477a9f883b0d919b84232022-12-21T23:31:50ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-02-01910.3389/fcell.2021.636544636544The Tumor Microenvironment in SCC: Mechanisms and Therapeutic OpportunitiesNádia Ghinelli Amôr0Paulo Sérgio da Silva Santos1Ana Paula Campanelli2Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, BrazilDepartment of Surgery, Stomatology, Pathology, and Radiology, Bauru School of Dentistry, University of São Paulo, Bauru, BrazilDepartment of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, BrazilSquamous cell carcinoma (SCC) is the second most common skin cancer worldwide and, despite the relatively easy visualization of the tumor in the clinic, a sizeable number of SCC patients are diagnosed at advanced stages with local invasion and distant metastatic lesions. In the last decade, immunotherapy has emerged as the fourth pillar in cancer therapy via the targeting of immune checkpoint molecules such as programmed cell-death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). FDA-approved monoclonal antibodies directed against these immune targets have provide survival benefit in a growing list of cancer types. Currently, there are two immunotherapy drugs available for cutaneous SCC: cemiplimab and pembrolizumab; both monoclonal antibodies (mAb) that block PD-1 thereby promoting T-cell activation and/or function. However, the success rate of these checkpoint inhibitors currently remains around 50%, which means that half of the patients with advanced SCC experience no benefit from this treatment. This review will highlight the mechanisms by which the immune checkpoint molecules regulate the tumor microenvironment (TME), as well as the ongoing clinical trials that are employing single or combinatory therapeutic approaches for SCC immunotherapy. We also discuss the regulation of additional pathways that might promote superior therapeutic efficacy, and consequently provide increased survival for those patients that do not benefit from the current checkpoint inhibitor therapies.https://www.frontiersin.org/articles/10.3389/fcell.2021.636544/fullcutaneous squamous cell carcinomaimmunotherapytumor microenvironmentcheckpoint inhibitorsregulatory T cellmacrophage |
| spellingShingle | Nádia Ghinelli Amôr Paulo Sérgio da Silva Santos Ana Paula Campanelli The Tumor Microenvironment in SCC: Mechanisms and Therapeutic Opportunities Frontiers in Cell and Developmental Biology cutaneous squamous cell carcinoma immunotherapy tumor microenvironment checkpoint inhibitors regulatory T cell macrophage |
| title | The Tumor Microenvironment in SCC: Mechanisms and Therapeutic Opportunities |
| title_full | The Tumor Microenvironment in SCC: Mechanisms and Therapeutic Opportunities |
| title_fullStr | The Tumor Microenvironment in SCC: Mechanisms and Therapeutic Opportunities |
| title_full_unstemmed | The Tumor Microenvironment in SCC: Mechanisms and Therapeutic Opportunities |
| title_short | The Tumor Microenvironment in SCC: Mechanisms and Therapeutic Opportunities |
| title_sort | tumor microenvironment in scc mechanisms and therapeutic opportunities |
| topic | cutaneous squamous cell carcinoma immunotherapy tumor microenvironment checkpoint inhibitors regulatory T cell macrophage |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.636544/full |
| work_keys_str_mv | AT nadiaghinelliamor thetumormicroenvironmentinsccmechanismsandtherapeuticopportunities AT paulosergiodasilvasantos thetumormicroenvironmentinsccmechanismsandtherapeuticopportunities AT anapaulacampanelli thetumormicroenvironmentinsccmechanismsandtherapeuticopportunities AT nadiaghinelliamor tumormicroenvironmentinsccmechanismsandtherapeuticopportunities AT paulosergiodasilvasantos tumormicroenvironmentinsccmechanismsandtherapeuticopportunities AT anapaulacampanelli tumormicroenvironmentinsccmechanismsandtherapeuticopportunities |