CD Markers
CD27
Copyright: 2003-2022, PathologyOutlines.com, Inc.
PubMed Search: CD27[TI] free full text[SB] pathology
CD27
Editorial Board Member: Patricia Tsang, M.D., M.B.A.
Deputy Editor-in-Chief: Genevieve M. Crane, M.D., Ph.D.
Last author update: 30 November 2020
Last staff update: 16 August 2022
Copyright: 2003-2022, PathologyOutlines.com, Inc.
PubMed Search: CD27[TI] free full text[SB] pathology
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Diagrams / tables | Clinical features | Interpretation | Uses by pathologists | Prognostic factors | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Flow cytometry images | Sample pathology report | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Bruehl F, Schürch CM. CD27. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cdmarkerscd27.html. Accessed December 1st, 2022.
Definition / general
- Tumor necrosis factor receptor family member expressed on T and B cells
Essential features
- CD27 is a costimulatory receptor of the TNF receptor superfamily expressed on lymphocytes
- CD27 is triggered by its unique ligand CD70, which is expressed on immune cells and often in cancers
- Soluble CD27 can be measured in serum and is an indicator of the CD70 - CD27 interaction in vivo
- CD27 deficiency should be considered in patients with immunodeficiencies and CD27 staining in flow cytometry can help detect immunodeficiencies
Terminology
- Also known as tumor necrosis factor receptor superfamily member 7 (TNFRSF7)
Pathophysiology
- CD27 is the receptor for its ligand CD70 (Int Immunol 1994;6:477)
- CD70 expression is tightly controlled in human tissues but often overexpressed in cancers (Pharmacol Ther 2015;155:1)
- CD27 is variably expressed on B, T and NK cells (J Immunol 1987;139:1589)
- CD27 is a costimulatory receptor (Int Immunol 1995;7:551)
- On T cells, CD27 activates NFκB and promotes cell survival, antigen receptor mediated proliferation and immune function (Curr Opin Immunol 2005;17:275)
- On B cells, CD27 augments Ig class switching and promotes plasma cell differentiation (Blood 2010;115:3051, Blood 1998;91:173)
- On NK cells, CD27 stimulates interferon gamma secretion (J Immunol 2000;164:1741)
- CD27 high and low NK cells represent functionally distinct subsets (J Immunol 2006;176:1517)
- On hematologic progenitor cells and leukemic stem cells, CD27 leads to Wnt pathway activation and promotes cell growth (J Clin Invest 2012;122:624)
- CD27 stimulation can lead to immune cell suppression depending on the duration and timing of signaling (Immunol Rev 2009;229:216)
- CD27 signaling increases the numbers of regulatory T cells and may promote tumor growth (Cancer Res 2012;72:3664)
- CD27 is a marker for IgG class switched memory (CD27+ IgD- IgM-) versus naïve B cells (CD27- IgD+ IgM+) (J Exp Med 1998;188:1679)
- Triggering of CD27 by CD70 leads to shedding of soluble CD27 from cells by a protease (J Immunol 1991;147:29)
- Soluble CD27 can be measured in serum and reflects the extent of CD27 / CD70 interactions in vivo (J Exp Med 2017;214:359)
Diagrams / tables
Clinical features
- Soluble CD27 has been explored as a promising marker of immune function and disease status in a range of infectious, immunologic and oncologic settings (J Immunol 2013;190:6250)
- Immunology
- CD27 deficiency can be seen in many cases of common variable immune deficiency (Blood 2002;99:1544)
- CD27 deficiency should be considered in all patients with hypogammaglobulinemia or unusually severe causes of EBV infection to allow for individualized treatment (J Allergy Clin Immunol 2012;129:787, Haematologica 2013;98:473)
- CD27 expression on lymphocytes is increased in patients with diffuse and limited cutaneous systemic sclerosis (Intractable Rare Dis Res 2020;9:99)
- High serum levels of soluble CD27 and increased CD27 negative memory B cells are associated with disease severity in systemic lupus erythematosus (Clin Rheumatol 1995;14:293, J Immunol 2007;178:6624)
- Oncology
- CD27 is being investigated as a therapeutic target for hematolymphoid malignancies and solid tumors (Blood Adv 2020;4:1917, J Clin Oncol 2017;35:2028)
- CAR T cells costimulated with CD27 signaling have improved survival and enhanced function in vitro and in vivo (Blood 2012;119:696)
Interpretation
- Membranous staining
Uses by pathologists
- CD27 dim expression detected by flow cytometry is a marker of atypical plasma cells (see Diagrams / tables)
- B cell phenotyping for evaluation of immunodeficiency syndromes and immune competence analysis by flow cytometry
- T cell phenotyping for evaluation of immunodeficiency syndromes and immune competence analysis by flow cytometry
Prognostic factors
- Solid tumors
- CD27 positive tumor infiltrating lymphocytes predict inferior survival in renal cell carcinoma (Clin Cancer Res 2015;21:889)
- CD27 negative tumor infiltrating lymphocytes are associated with an improved survival in high grade serous ovarian carcinoma (Clin Cancer Res 2012;18:3281)
- CD27 negative tumor infiltrating lymphocytes are associated with an improved survival in hepatocellular carcinoma (Clin Cancer Res 2013;19:5994)
- Hematolymphoid neoplasms
- Soluble CD27 is an independent negative prognostic marker in acute myeloid leukemia (J Exp Med 2017;214:359)
- CD27 is highly expressed in high risk B cell progenitor acute lymphoblastic leukemia and associated with decreased survival (Blood Cancer J 2017;7:e575)
- CD27 expression indicates poor prognosis in multiple myeloma (Clin Immunol 2020;213:108363)
Microscopic (histologic) images
Contributed by Christian Schürch, M.D., Ph.D.
Immunohistochemical
double staining
(CD27 and CD34)
Positive staining - normal
- Immune cells (see Pathophysiology)
Positive staining - disease
- Myeloma (heterogeneous expression) (Br J Haematol 2006;132:168, Br J Haematol 2003;121:36)
- Adult T cell leukemia / lymphoma (100%, 17/17) (Am J Clin Pathol 2010;133:592)
- Chronic lymphocytic leukemia (100%, 18/18) (Blood 1995;85:3556)
- Mantle cell lymphoma (100%, 15/15) (Leuk Lymphoma 2002;43:1855)
- Burkitt lymphoma (100%, 6/6) (Leuk Lymphoma 2002;43:1855)
- Pro B acute lymphoblastic leukemia (Leuk Lymphoma 2002;43:1855, Exp Hematol 2005;33:1500)
- CD27 positive hairy cell leukemia, Japanese variant (Virchows Arch 2016;468:375)
- Chronic myeloid leukemia, CD34 positive blasts (J Clin Invest 2012;122:624)
Negative staining
- Oncology
- Hairy cell leukemia (Haematologica 2005;90:266)
- Splenic diffuse red pulp lymphoma (Clin Lymphoma Myeloma Leuk 2016;16:S166)
- Immunology
- Chronic active EBV infection associated with CD27 deficiency (J Allergy Clin Immunol 2015;136:703)
Flow cytometry images
Contributed by Frido Bruehl, M.D. and Betty Gay, B.S.
Flow cytometry of CVID patient
Sample pathology report
- Peripheral blood, flow cytometry, quantitative B cell phenotyping analysis:
- Abnormal (see comment)
- Comment: A decrease of class switched memory B cells (CD19 positive, CD27 positive, IgM negative, IgD negative) is consistent with common variable immunodeficiency (CVID). Switched memory B cells are quantitatively decreased in relation to marginal zone B cells (CD19 positive, CD27 positive, IgM positive, IgD negative). This result is consistent with but not diagnostic of CVID. Quantitative B cell phenotyping is helpful for the classification and prognosis of CVID and should be considered in the context of clinical and other immunological and laboratory findings. Decreased class switched memory B cells may also be seen in some autoimmune diseases, secondary to certain medications and in patients with other hereditary syndromes.
Additional references
Board review style question #1
Which statement about CD27 is true?
- CD27 shows nuclear expression
- CD27 is constitutively expressed in nonlymphoid tissues
- CD27 is not expressed on myeloid precursor cells
- CD70, the ligand of CD27, is often overexpressed in cancer
- There are no current clinical uses of CD27
Board review style answer #1
D. CD70 is overexpressed in many cancers and the CD27 / CD70 immune axis is utilized by cancers to escape immune surveillance (Oncoimmunology 2012;1:1604)
Comment Here
Reference: CD27
Comment Here
Reference: CD27
