Cargando…

Prevalence of CD8(+) cytotoxic lymphocytes in human neoplasms

PURPOSE: Immune checkpoint inhibitors have recently been approved by the US FDA as first and/or second line therapy in a subset of cancer types. Recent evidence suggests that the quantity of tumor infiltrating lymphocytes (TILs) influences the likelihood of response to immune checkpoint inhibitors....

Descripción completa

Detalles Bibliográficos
Autores principales: Blessin, Niclas C., Spriestersbach, Patrick, Li, Wenchao, Mandelkow, Tim, Dum, David, Simon, Ronald, Hube-Magg, Claudia, Lutz, Florian, Viehweger, Florian, Lennartz, Maximillian, Fraune, Christoph, Nickelsen, Vera, Fehrle, Wilfried, Göbel, Cosima, Weidemann, Sören, Clauditz, Till, Lebok, Patrick, Möller, Katharina, Steurer, Stefan, Izbicki, Jacob R., Sauter, Guido, Minner, Sarah, Jacobsen, Frank, Luebke, Andreas M., Büscheck, Franziska, Höflmayer, Doris, Wilczak, Waldemar, Burandt, Eike, Hinsch, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214387/
https://www.ncbi.nlm.nih.gov/pubmed/32141029
http://dx.doi.org/10.1007/s13402-020-00496-7
_version_ 1783531959257923584
author Blessin, Niclas C.
Spriestersbach, Patrick
Li, Wenchao
Mandelkow, Tim
Dum, David
Simon, Ronald
Hube-Magg, Claudia
Lutz, Florian
Viehweger, Florian
Lennartz, Maximillian
Fraune, Christoph
Nickelsen, Vera
Fehrle, Wilfried
Göbel, Cosima
Weidemann, Sören
Clauditz, Till
Lebok, Patrick
Möller, Katharina
Steurer, Stefan
Izbicki, Jacob R.
Sauter, Guido
Minner, Sarah
Jacobsen, Frank
Luebke, Andreas M.
Büscheck, Franziska
Höflmayer, Doris
Wilczak, Waldemar
Burandt, Eike
Hinsch, Andrea
author_facet Blessin, Niclas C.
Spriestersbach, Patrick
Li, Wenchao
Mandelkow, Tim
Dum, David
Simon, Ronald
Hube-Magg, Claudia
Lutz, Florian
Viehweger, Florian
Lennartz, Maximillian
Fraune, Christoph
Nickelsen, Vera
Fehrle, Wilfried
Göbel, Cosima
Weidemann, Sören
Clauditz, Till
Lebok, Patrick
Möller, Katharina
Steurer, Stefan
Izbicki, Jacob R.
Sauter, Guido
Minner, Sarah
Jacobsen, Frank
Luebke, Andreas M.
Büscheck, Franziska
Höflmayer, Doris
Wilczak, Waldemar
Burandt, Eike
Hinsch, Andrea
author_sort Blessin, Niclas C.
collection PubMed
description PURPOSE: Immune checkpoint inhibitors have recently been approved by the US FDA as first and/or second line therapy in a subset of cancer types. Recent evidence suggests that the quantity of tumor infiltrating lymphocytes (TILs) influences the likelihood of response to immune checkpoint inhibitors. Here, we set out to assess the density of CD8(+) lymphocytes in a wide range of different cancer types and subtypes. METHODS: The density of CD8(+) lymphocytes was compared across different cancer types using tissue microarrays (TMAs) composed of up to 50 tumor samples each from 84 different cancer types and subtypes. In total 2652 cancers and 608 normal tissues were successfully analyzed by CD8 immunohistochemistry followed by automated image analysis of digitized slides. RESULTS: We found that the median CD8(+) lymphocyte counts ranged from 6 cells/mm(2) in pleomorphic adenoma up to 1573 cells/mm(2) in Hodgkin’s lymphoma. The CD8 counts were generally lower in normal tissues compared to cancer tissues. Blood vessels of the spleen were the only non-lymphatic tissue staining positive for CD8. Tumor types approved for checkpoint inhibitor therapy, including malignant melanoma (81), muscle invasive urothelial carcinoma (119), small cell lung cancer (120), clear cell renal cell cancer (153), squamous cell carcinoma (189) and adenocarcinoma of the lung (328) as well as Hodgkin’s lymphoma (1573) were all ranking among the upper half of our list. Comparably high CD8 densities (median cells/mm(2)) were also found in several rare and aggressive cancer types including Merkel cell carcinoma (70), angiosarcoma (95), anaplastic thyroid cancer (156) and embryonal carcinoma of the testis (186). In 73 of the 84 analyzed cancer types, the highly variable CD8 counts occasionally exceeded the average CD8 count of tumors for which checkpoint inhibitors have been approved. CONCLUSION: These data support the concept that among most tumor types at least some individual cancers may benefit from treatment with immune checkpoint inhibitors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13402-020-00496-7) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-7214387
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Springer Netherlands
record_format MEDLINE/PubMed
spelling pubmed-72143872020-05-14 Prevalence of CD8(+) cytotoxic lymphocytes in human neoplasms Blessin, Niclas C. Spriestersbach, Patrick Li, Wenchao Mandelkow, Tim Dum, David Simon, Ronald Hube-Magg, Claudia Lutz, Florian Viehweger, Florian Lennartz, Maximillian Fraune, Christoph Nickelsen, Vera Fehrle, Wilfried Göbel, Cosima Weidemann, Sören Clauditz, Till Lebok, Patrick Möller, Katharina Steurer, Stefan Izbicki, Jacob R. Sauter, Guido Minner, Sarah Jacobsen, Frank Luebke, Andreas M. Büscheck, Franziska Höflmayer, Doris Wilczak, Waldemar Burandt, Eike Hinsch, Andrea Cell Oncol (Dordr) Article PURPOSE: Immune checkpoint inhibitors have recently been approved by the US FDA as first and/or second line therapy in a subset of cancer types. Recent evidence suggests that the quantity of tumor infiltrating lymphocytes (TILs) influences the likelihood of response to immune checkpoint inhibitors. Here, we set out to assess the density of CD8(+) lymphocytes in a wide range of different cancer types and subtypes. METHODS: The density of CD8(+) lymphocytes was compared across different cancer types using tissue microarrays (TMAs) composed of up to 50 tumor samples each from 84 different cancer types and subtypes. In total 2652 cancers and 608 normal tissues were successfully analyzed by CD8 immunohistochemistry followed by automated image analysis of digitized slides. RESULTS: We found that the median CD8(+) lymphocyte counts ranged from 6 cells/mm(2) in pleomorphic adenoma up to 1573 cells/mm(2) in Hodgkin’s lymphoma. The CD8 counts were generally lower in normal tissues compared to cancer tissues. Blood vessels of the spleen were the only non-lymphatic tissue staining positive for CD8. Tumor types approved for checkpoint inhibitor therapy, including malignant melanoma (81), muscle invasive urothelial carcinoma (119), small cell lung cancer (120), clear cell renal cell cancer (153), squamous cell carcinoma (189) and adenocarcinoma of the lung (328) as well as Hodgkin’s lymphoma (1573) were all ranking among the upper half of our list. Comparably high CD8 densities (median cells/mm(2)) were also found in several rare and aggressive cancer types including Merkel cell carcinoma (70), angiosarcoma (95), anaplastic thyroid cancer (156) and embryonal carcinoma of the testis (186). In 73 of the 84 analyzed cancer types, the highly variable CD8 counts occasionally exceeded the average CD8 count of tumors for which checkpoint inhibitors have been approved. CONCLUSION: These data support the concept that among most tumor types at least some individual cancers may benefit from treatment with immune checkpoint inhibitors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13402-020-00496-7) contains supplementary material, which is available to authorized users. Springer Netherlands 2020-03-05 2020 /pmc/articles/PMC7214387/ /pubmed/32141029 http://dx.doi.org/10.1007/s13402-020-00496-7 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Blessin, Niclas C.
Spriestersbach, Patrick
Li, Wenchao
Mandelkow, Tim
Dum, David
Simon, Ronald
Hube-Magg, Claudia
Lutz, Florian
Viehweger, Florian
Lennartz, Maximillian
Fraune, Christoph
Nickelsen, Vera
Fehrle, Wilfried
Göbel, Cosima
Weidemann, Sören
Clauditz, Till
Lebok, Patrick
Möller, Katharina
Steurer, Stefan
Izbicki, Jacob R.
Sauter, Guido
Minner, Sarah
Jacobsen, Frank
Luebke, Andreas M.
Büscheck, Franziska
Höflmayer, Doris
Wilczak, Waldemar
Burandt, Eike
Hinsch, Andrea
Prevalence of CD8(+) cytotoxic lymphocytes in human neoplasms
title Prevalence of CD8(+) cytotoxic lymphocytes in human neoplasms
title_full Prevalence of CD8(+) cytotoxic lymphocytes in human neoplasms
title_fullStr Prevalence of CD8(+) cytotoxic lymphocytes in human neoplasms
title_full_unstemmed Prevalence of CD8(+) cytotoxic lymphocytes in human neoplasms
title_short Prevalence of CD8(+) cytotoxic lymphocytes in human neoplasms
title_sort prevalence of cd8(+) cytotoxic lymphocytes in human neoplasms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214387/
https://www.ncbi.nlm.nih.gov/pubmed/32141029
http://dx.doi.org/10.1007/s13402-020-00496-7
work_keys_str_mv AT blessinniclasc prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT spriestersbachpatrick prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT liwenchao prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT mandelkowtim prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT dumdavid prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT simonronald prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT hubemaggclaudia prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT lutzflorian prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT viehwegerflorian prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT lennartzmaximillian prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT fraunechristoph prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT nickelsenvera prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT fehrlewilfried prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT gobelcosima prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT weidemannsoren prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT clauditztill prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT lebokpatrick prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT mollerkatharina prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT steurerstefan prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT izbickijacobr prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT sauterguido prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT minnersarah prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT jacobsenfrank prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT luebkeandreasm prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT buscheckfranziska prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT hoflmayerdoris prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT wilczakwaldemar prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT burandteike prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms
AT hinschandrea prevalenceofcd8cytotoxiclymphocytesinhumanneoplasms