Case Report: Sustained Remission Due to PD-1-Inhibition in a Metastatic Melanoma Patient With Depleted B Cells
IntroductionCheckpoint-Inhibition (CPI) with PD-1- and PD-L1-inhibitors is a well-established therapy for advanced stage melanoma patients. CPI mainly acts via T-lymphocytes. However, recent literature suggests also a role for B cells modulating its efficacy and tolerability of CPI.Case ReportWe rep...
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doaj-60633f4630ff4b78a6fe51d23dfaff1e2021-10-05T13:00:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.733961733961Case Report: Sustained Remission Due to PD-1-Inhibition in a Metastatic Melanoma Patient With Depleted B CellsLena Margarethe Wulfken0Jürgen Christian Becker1Jürgen Christian Becker2Jürgen Christian Becker3Jürgen Christian Becker4Rami Hayajneh5Rami Hayajneh6Rami Hayajneh7Rami Hayajneh8Annette Doris Wagner9Katrin Schaper-Gerhardt10Katrin Schaper-Gerhardt11Nina Flatt12Imke Grimmelmann13Ralf Gutzmer14Ralf Gutzmer15Skin Cancer Center Hannover, Department of Dermatology and Allergy, Hannover Medical School, Hannover, GermanyTranslational Skin Cancer Research (TSCR), University Duisburg-Essen, Essen, GermanyGerman Cancer Consortium (DKTK) & German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Dermatology, University Hospital Essen, Essen, GermanyCenter for Medical Biology, Essen, GermanyTranslational Skin Cancer Research (TSCR), University Duisburg-Essen, Essen, GermanyGerman Cancer Consortium (DKTK) & German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Dermatology, University Hospital Essen, Essen, GermanyCenter for Medical Biology, Essen, GermanyClinic for Kidney and Hypertension Diseases, Hannover Medical School, Hannover, GermanySkin Cancer Center Hannover, Department of Dermatology and Allergy, Hannover Medical School, Hannover, GermanyDepartment of Dermatology, Ruhr University Bochum, Minden, GermanySkin Cancer Center Hannover, Department of Dermatology and Allergy, Hannover Medical School, Hannover, GermanySkin Cancer Center Hannover, Department of Dermatology and Allergy, Hannover Medical School, Hannover, GermanySkin Cancer Center Hannover, Department of Dermatology and Allergy, Hannover Medical School, Hannover, GermanyDepartment of Dermatology, Ruhr University Bochum, Minden, GermanyIntroductionCheckpoint-Inhibition (CPI) with PD-1- and PD-L1-inhibitors is a well-established therapy for advanced stage melanoma patients. CPI mainly acts via T-lymphocytes. However, recent literature suggests also a role for B cells modulating its efficacy and tolerability of CPI.Case ReportWe report a 48-year-old female patient with metastatic melanoma affecting brain, lung, skin and lymph nodes. A preexisting granulomatosis with polyangiitis was treated with rituximab over five years prior to the diagnosis of melanoma, resulting in a complete depletion of B cells both in peripheral blood as well as the tumor tissue. In the absence of the mutation of the proto-oncogene b-raf, treatment with the PD-1 inhibitor nivolumab was initiated. This therapy was well tolerated and resulted in a deep partial response, which is ongoing for 14+ months. Flow cytometric analysis of peripheral blood mononuclear cells revealed 15% IL-10 producing and 14% CD24 and CD38 double positive regulatory B cells.ConclusionThe exceptional clinical response to nivolumab monotherapy in our patient with depleted B cells sheds a new light on the relevance of B cells in the modulation of immune responses to melanoma. Obviously, B cells were not required for the efficacy of CPI in our patient. Moreover, the depletion of regulatory B cells may have improved efficacy of CPI.https://www.frontiersin.org/articles/10.3389/fimmu.2021.733961/fullcase reportB cell depletionimmune checkpoint blockadeCD20melanoma |
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language |
English |
format |
Article |
sources |
DOAJ |
author |
Lena Margarethe Wulfken Jürgen Christian Becker Jürgen Christian Becker Jürgen Christian Becker Jürgen Christian Becker Rami Hayajneh Rami Hayajneh Rami Hayajneh Rami Hayajneh Annette Doris Wagner Katrin Schaper-Gerhardt Katrin Schaper-Gerhardt Nina Flatt Imke Grimmelmann Ralf Gutzmer Ralf Gutzmer |
spellingShingle |
Lena Margarethe Wulfken Jürgen Christian Becker Jürgen Christian Becker Jürgen Christian Becker Jürgen Christian Becker Rami Hayajneh Rami Hayajneh Rami Hayajneh Rami Hayajneh Annette Doris Wagner Katrin Schaper-Gerhardt Katrin Schaper-Gerhardt Nina Flatt Imke Grimmelmann Ralf Gutzmer Ralf Gutzmer Case Report: Sustained Remission Due to PD-1-Inhibition in a Metastatic Melanoma Patient With Depleted B Cells Frontiers in Immunology case report B cell depletion immune checkpoint blockade CD20 melanoma |
author_facet |
Lena Margarethe Wulfken Jürgen Christian Becker Jürgen Christian Becker Jürgen Christian Becker Jürgen Christian Becker Rami Hayajneh Rami Hayajneh Rami Hayajneh Rami Hayajneh Annette Doris Wagner Katrin Schaper-Gerhardt Katrin Schaper-Gerhardt Nina Flatt Imke Grimmelmann Ralf Gutzmer Ralf Gutzmer |
author_sort |
Lena Margarethe Wulfken |
title |
Case Report: Sustained Remission Due to PD-1-Inhibition in a Metastatic Melanoma Patient With Depleted B Cells |
title_short |
Case Report: Sustained Remission Due to PD-1-Inhibition in a Metastatic Melanoma Patient With Depleted B Cells |
title_full |
Case Report: Sustained Remission Due to PD-1-Inhibition in a Metastatic Melanoma Patient With Depleted B Cells |
title_fullStr |
Case Report: Sustained Remission Due to PD-1-Inhibition in a Metastatic Melanoma Patient With Depleted B Cells |
title_full_unstemmed |
Case Report: Sustained Remission Due to PD-1-Inhibition in a Metastatic Melanoma Patient With Depleted B Cells |
title_sort |
case report: sustained remission due to pd-1-inhibition in a metastatic melanoma patient with depleted b cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-10-01 |
description |
IntroductionCheckpoint-Inhibition (CPI) with PD-1- and PD-L1-inhibitors is a well-established therapy for advanced stage melanoma patients. CPI mainly acts via T-lymphocytes. However, recent literature suggests also a role for B cells modulating its efficacy and tolerability of CPI.Case ReportWe report a 48-year-old female patient with metastatic melanoma affecting brain, lung, skin and lymph nodes. A preexisting granulomatosis with polyangiitis was treated with rituximab over five years prior to the diagnosis of melanoma, resulting in a complete depletion of B cells both in peripheral blood as well as the tumor tissue. In the absence of the mutation of the proto-oncogene b-raf, treatment with the PD-1 inhibitor nivolumab was initiated. This therapy was well tolerated and resulted in a deep partial response, which is ongoing for 14+ months. Flow cytometric analysis of peripheral blood mononuclear cells revealed 15% IL-10 producing and 14% CD24 and CD38 double positive regulatory B cells.ConclusionThe exceptional clinical response to nivolumab monotherapy in our patient with depleted B cells sheds a new light on the relevance of B cells in the modulation of immune responses to melanoma. Obviously, B cells were not required for the efficacy of CPI in our patient. Moreover, the depletion of regulatory B cells may have improved efficacy of CPI. |
topic |
case report B cell depletion immune checkpoint blockade CD20 melanoma |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.733961/full |
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