Pathology Outlines

CD Markers
CD27

Authors: Frido Bruehl, M.D., Christian M. Schürch, M.D., Ph.D.

Editorial Board Member: Patricia Tsang, M.D., M.B.A.

Deputy Editor-in-Chief: Genevieve M. Crane, M.D., Ph.D.

Topic Completed: 30 November 2020

Minor changes: 14 May 2021

Copyright: 2003-2021, PathologyOutlines.com, Inc.

PubMed Search: CD27[TI] free full text[SB] pathology

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Table of Contents

Cite this page: Bruehl F, Schürch CM. CD27. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cdmarkerscd27.html. Accessed November 27th, 2021.

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

Images hosted on other servers:

CD27 signaling in different cancer settings

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

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

OMIM: CD27 Antigen [Accessed 06 July 2020]

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