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Expression of PD-1,...
Expression of PD-1, PD-L1 and PD-L2 in Lymphomas in Patients with Pre-Existing Rheumatic Diseases-A Possible Association with High Rheumatoid Arthritis Disease Activity
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- Hellbacher, Erik (author)
- Uppsala universitet,Reumatologi
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- Sundström, Christer (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab
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- Molin, Daniel, 1969- (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Baecklund, Eva, 1956- (author)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Hollander, Peter (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Klinisk och experimentell patologi
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(creator_code:org_t)
- 2022-03-15
- 2022
- English.
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In: Cancers. - : MDPI. - 2072-6694. ; 14:6
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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Abstract
Subject headings
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- Simple Summary Immunotherapy blocking programmed cell death protein 1 (PD-1) and its ligands (PD-L1, PD-L2) is less effective in non-Hodgkin lymphoma (NHL) than classical Hodgkin lymphoma. However, NHL is a heterogeneous group and current research seeks to identify subgroups of NHL patients responsive to PD-1 blocking agents. Whether patients with pre-existing rheumatic diseases might constitute such a subgroup is unknown. We investigated the expression of PD-1 and its ligands in lymphoma patients with pre-existing rheumatic diseases. Our key findings include that in patients with pre-existing rheumatoid arthritis (RA) and subsequent diffuse large B-cell lymphoma, an association between RA disease severity and increased expression of PD-L1 in tumor cells was seen. This warrants further studies of the PD-1 pathway in lymphoma in other chronic inflammatory conditions. Current research seeks to identify subgroups of non-Hodgkin lymphoma (NHL) patients responsive to PD-1 blocking agents. Whether patients with pre-existing rheumatic diseases might constitute such a subgroup is unknown. We determined intratumoral expression of PD-1 and its ligands in lymphoma patients with pre-existing rheumatic diseases. We included 215 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or Sjogren's syndrome with subsequent lymphoma and 74 diffuse large B-cell lymphoma (DLBCL) controls without rheumatic disease. PD-1 and PD-ligand immunohistochemical markers were applied on tumor tissue microarrays. The number of PD-1+ tumor infiltrating leukocytes (TILs) and proportions of PD-L1+ and PD-L2+ tumor cells and TILs were calculated and correlated with clinical data. Expression of PD-L1 in tumor cells and TILs was highest in classical Hodgkin lymphoma and DLBCL. In DLBCLs, expression of PD-1 in TILs and PD-L1 in tumor cells was similar in RA, SLE and controls. In RA-DLBCL, high expression of PD-L1 in tumor cells was significantly more common in patients with the most severe RA disease and was associated with inferior overall survival in multivariable analysis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- lymphoma
- PD-1
- PD-L1
- rheumatic disease
- immunohistochemistry
Publication and Content Type
- ref (subject category)
- art (subject category)
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