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Resistance to anti-PD-1-based immunotherapy in basal cell carcinoma: a case report and review of the literature

BACKGROUND: Immunotherapy with immune checkpoint inhibitors has radically changed the management of a broad spectrum of tumors. In contrast, only very limited information is available about the efficacy of these therapies in non-melanoma skin cancers, especially in basal cell carcinoma. The latter m...

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Autores principales: Sabbatino, Francesco, Marra, Antonio, Liguori, Luigi, Scognamiglio, Giosuè, Fusciello, Celeste, Botti, Gerardo, Ferrone, Soldano, Pepe, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247622/
https://www.ncbi.nlm.nih.gov/pubmed/30458852
http://dx.doi.org/10.1186/s40425-018-0439-2
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author Sabbatino, Francesco
Marra, Antonio
Liguori, Luigi
Scognamiglio, Giosuè
Fusciello, Celeste
Botti, Gerardo
Ferrone, Soldano
Pepe, Stefano
author_facet Sabbatino, Francesco
Marra, Antonio
Liguori, Luigi
Scognamiglio, Giosuè
Fusciello, Celeste
Botti, Gerardo
Ferrone, Soldano
Pepe, Stefano
author_sort Sabbatino, Francesco
collection PubMed
description BACKGROUND: Immunotherapy with immune checkpoint inhibitors has radically changed the management of a broad spectrum of tumors. In contrast, only very limited information is available about the efficacy of these therapies in non-melanoma skin cancers, especially in basal cell carcinoma. The latter malignancy is often associated with both an impairment of the host immune response and a high mutation burden, suggesting that immune checkpoint inhibitor-based immunotherapy may be effective in the treatment of this tumor. CASE PRESENTATION: A 78-year-old woman was diagnosed with a metastatic non-small-cell-lung-cancer. Following the lack of response to two lines of systemic chemotherapy, she was treated with the anti-PD-1 monoclonal antibody nivolumab, obtaining a prolonged stable disease. Under nivolumab treatment, the patient developed a basal cell carcinoma of the nose. The latter was surgically resected. Immunohistochemical staining of tumor tissue showed a PD-L1 expression < 1% and lack of human leukocyte antigen class I subunit (i.e. heavy and light chain) expression on tumor cells. In addition, a limited number of T cells (CD3+) was present in the tumor microenvironment, with a higher number of regulatory T cells (Foxp3+) and macrophages (Cd11b+) as compared to a low infiltration of activated cytotoxic T cells (CD8+/ Granzyme B+). Two months following the surgical removal of the tumor, while still on nivolumab treatment, the patient relapsed with a basal cell carcinoma in the same anatomic site of the previous surgical excision. The tumor displayed the same pathological characteristics. CONCLUSION: Preclinical lines of evidence suggest a potential role of immune checkpoint inhibitors for basal cell carcinoma treatment. However, limited clinical data is available. In the patient we have described administration of the immune checkpoint inhibitor nivolumab for the treatment of a responsive non-small cell carcinoma was associated with the development and relapse of a basal cell carcinoma tumor. This association is likely to reflect the resistance of basal cell carcinoma cells to anti-PD-1 based immunotherapy because of a “cold” tumor microenvironment characterized by lack of human leukocyte antigen class I expression, low PD-L1 expression and high number of immune regulatory cells.
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spelling pubmed-62476222018-11-26 Resistance to anti-PD-1-based immunotherapy in basal cell carcinoma: a case report and review of the literature Sabbatino, Francesco Marra, Antonio Liguori, Luigi Scognamiglio, Giosuè Fusciello, Celeste Botti, Gerardo Ferrone, Soldano Pepe, Stefano J Immunother Cancer Case Report BACKGROUND: Immunotherapy with immune checkpoint inhibitors has radically changed the management of a broad spectrum of tumors. In contrast, only very limited information is available about the efficacy of these therapies in non-melanoma skin cancers, especially in basal cell carcinoma. The latter malignancy is often associated with both an impairment of the host immune response and a high mutation burden, suggesting that immune checkpoint inhibitor-based immunotherapy may be effective in the treatment of this tumor. CASE PRESENTATION: A 78-year-old woman was diagnosed with a metastatic non-small-cell-lung-cancer. Following the lack of response to two lines of systemic chemotherapy, she was treated with the anti-PD-1 monoclonal antibody nivolumab, obtaining a prolonged stable disease. Under nivolumab treatment, the patient developed a basal cell carcinoma of the nose. The latter was surgically resected. Immunohistochemical staining of tumor tissue showed a PD-L1 expression < 1% and lack of human leukocyte antigen class I subunit (i.e. heavy and light chain) expression on tumor cells. In addition, a limited number of T cells (CD3+) was present in the tumor microenvironment, with a higher number of regulatory T cells (Foxp3+) and macrophages (Cd11b+) as compared to a low infiltration of activated cytotoxic T cells (CD8+/ Granzyme B+). Two months following the surgical removal of the tumor, while still on nivolumab treatment, the patient relapsed with a basal cell carcinoma in the same anatomic site of the previous surgical excision. The tumor displayed the same pathological characteristics. CONCLUSION: Preclinical lines of evidence suggest a potential role of immune checkpoint inhibitors for basal cell carcinoma treatment. However, limited clinical data is available. In the patient we have described administration of the immune checkpoint inhibitor nivolumab for the treatment of a responsive non-small cell carcinoma was associated with the development and relapse of a basal cell carcinoma tumor. This association is likely to reflect the resistance of basal cell carcinoma cells to anti-PD-1 based immunotherapy because of a “cold” tumor microenvironment characterized by lack of human leukocyte antigen class I expression, low PD-L1 expression and high number of immune regulatory cells. BioMed Central 2018-11-20 /pmc/articles/PMC6247622/ /pubmed/30458852 http://dx.doi.org/10.1186/s40425-018-0439-2 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Case Report
Sabbatino, Francesco
Marra, Antonio
Liguori, Luigi
Scognamiglio, Giosuè
Fusciello, Celeste
Botti, Gerardo
Ferrone, Soldano
Pepe, Stefano
Resistance to anti-PD-1-based immunotherapy in basal cell carcinoma: a case report and review of the literature
title Resistance to anti-PD-1-based immunotherapy in basal cell carcinoma: a case report and review of the literature
title_full Resistance to anti-PD-1-based immunotherapy in basal cell carcinoma: a case report and review of the literature
title_fullStr Resistance to anti-PD-1-based immunotherapy in basal cell carcinoma: a case report and review of the literature
title_full_unstemmed Resistance to anti-PD-1-based immunotherapy in basal cell carcinoma: a case report and review of the literature
title_short Resistance to anti-PD-1-based immunotherapy in basal cell carcinoma: a case report and review of the literature
title_sort resistance to anti-pd-1-based immunotherapy in basal cell carcinoma: a case report and review of the literature
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247622/
https://www.ncbi.nlm.nih.gov/pubmed/30458852
http://dx.doi.org/10.1186/s40425-018-0439-2
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