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F1000Res. 2016 Jan 08;5:38. doi: 10.12688/f1000research.7599.1. eCollection 2016.

Rituximab efficiently depletes B cells in lung tumors and normal lung tissue.

F1000Research

Albane Joly-Battaglini, Clara Hammarström, Branislava Stankovic, Henrik Aamodt, Johan Stjärne, Odd Terje Brustugun, Åslaug Helland, Inger Øynebråten, Alexandre Corthay

Affiliations

  1. Tumor Immunology group, Department of Pathology, Oslo University Hospital, Oslo, Norway; Centre for Immune Regulation, University of Oslo, Oslo, Norway.
  2. Department of Pathology, Oslo University Hospital, Oslo, Norway.
  3. Tumor Immunology group, Department of Pathology, Oslo University Hospital, Oslo, Norway; Centre for Immune Regulation, University of Oslo, Oslo, Norway; Department of Cardiothoracic Surgery, Oslo University Hospital, Oslo, Norway.
  4. Betanien Hospital, Skien, Norway.
  5. Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
  6. Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Department of Cancer Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
  7. Tumor Immunology group, Department of Pathology, Oslo University Hospital, Oslo, Norway; Centre for Immune Regulation, University of Oslo, Oslo, Norway; Department of Biosciences, University of Oslo, Oslo, Norway.

PMID: 27081474 PMCID: PMC4813631 DOI: 10.12688/f1000research.7599.1

Abstract

Rituximab is a monoclonal antibody that targets the CD20 B-cell-specific antigen and is widely used as therapy for B-cell lymphoma. Since rituximab depletes both malignant and normal B cells, it is increasingly being used to treat various conditions in which normal B cells have a pathogenic role, such as rheumatoid arthritis and multiple sclerosis. It is well-established that rituximab efficiently eliminates B cells in blood, lymph nodes, and spleen. In contrast, the effect of rituximab in non-lymphoid tissues remains poorly documented and is debated. Here, we report a rheumatoid arthritis patient who was treated with rituximab before receiving thoracic surgery for non-small cell lung cancer. Using flow cytometry and immunohistochemistry, we show that rituximab efficiently depleted CD20-positive B cells in a primary lung tumor, in lung-associated lymph nodes, and in normal lung tissue. We conclude that rituximab may be very efficient at depleting normal B cells in the lungs. This property of rituximab may potentially be exploited for the treatment of conditions in which pathogenic B cells reside in the lungs. On the other hand, the clearance of lung B cells may provide an explanation for the rare cases of severe non-infectious pulmonary toxicity of rituximab.

Keywords: B cells; depletion; lungs; lymph node; monoclonal antibody; non-small cell lung cancer; rituximab; tumor

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