Stains & CD markers
CD70
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: CD70 pathology
CD70
Editorial Board Member: Patricia Tsang, M.D., M.B.A.
Deputy Editor-in-Chief: Genevieve M. Crane, M.D., Ph.D.
Last author update: 2 March 2023
Last staff update: 2 March 2023
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: CD70 pathology
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Clinical features | Interpretation | Uses by pathologists | Prognostic factors | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Board review style question #1 | Board review style answer #1Cite this page: Bruehl F, Schürch CM. CD70. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cdmarkerscd70.html. Accessed April 26th, 2024.
Definition / general
- Ligand to CD27 that is transiently upregulated upon stimulation of immune cells and delivers a costimulatory signal to T cells
Essential features
- Transmembrane protein and unique ligand to CD27
- Expressed on lymphocytes and dendritic cells (Curr Opin Immunol 2005;17:275)
- Provides stimulatory signal for T cell development and activation (Curr Opin Immunol 2005;17:275)
- Provides complex (and incompletely understood) signaling for B cell development (Semin Arthritis Rheum 2016;45:496)
- Expressed on various solid tumors and hematolymphoid malignancies and may impart a poor prognosis
Terminology
- Tumor necrosis factor ligand superfamily member 7 (TNFSF7)
- CD27 ligand (CD27L)
- Ki24 antigen (Blood 1985;66:848)
Pathophysiology
- Transiently upregulated during lymphocyte activation (J Immunol 1994;152:1756)
- Regulated by activation signals received via toll-like receptors (TLRs), CD40 and the antigen receptor MHC II (Semin Arthritis Rheum 2016;45:496)
- Only characterized ligand to CD27 with bidirectional signaling activity
- Can be upregulated on leukemia cells after tyrosine kinase inhibitor therapy (Sci Transl Med 2015;7:298ra119)
- Reverse signaling through CD70 enhances NK cell function and immunosurveillance of CD27 expressing B cell malignancies (Blood 2017;130:297)
- Regulatory T cells can gain CD70 expression after prolonged stimulation, curbing their suppressive activity on other T cells (Commun Biol 2020;3:375)
Clinical features
- Targeting CD70 has shown promise in xenograft models and a phase 1 study using the monoclonal antibody cusatuzumab (Blood 2011;117:4304, Nat Med 2020;26:1459)
- Genetic polymorphisms in CD70 may cause susceptibility to EBV driven malignancies (J Exp Med 2017;214:91)
- CD70 specific CAR T cells show anti-AML activity in murine AML xenograft models (Blood 2021;138:318, J Immunother Cancer 2022;10:e003289)
Interpretation
- Membranous and cytoplasmic staining (Clin Cancer Res 2008;14:7763)
Uses by pathologists
- No current clinical use by pathologists
Prognostic factors
- High CD70 expression is associated with poor overall survival in
- Glioblastoma (Int J Cancer 2017;141:1434)
- Ovarian serous carcinoma (Onco Targets Ther 2013;6:615)
- Pleural mesothelioma (J Pathol 2020;250:205)
Microscopic (histologic) images
Contributed by Christian Schürch, M.D., Ph.D.
Bone marrow biopsy
Positive staining - normal
- Temporarily expressed on activated T and B cells (Eur J Immunol 1996;26:2964)
- Stromal cells of thymic medulla (Int Immunol 1994;6:477)
- NK cells (J Immunol 1999;163:5358)
Positive staining - disease
- B cell lymphomas
- Expressed on chronic lymphocytic leukemia cells (89%, 17/19) (Blood 1995;85:3556)
- Diffuse large B cell lymphoma (Genes Chromosomes Cancer 2013;52:764)
- Follicular lymphoma (77%, 20/26) (Invest New Drugs 2019;37:297)
- Waldenström macroglobulinemia (100%, 6/6) (Blood 2008;112:4683)
- Hodgkin lymphoma (Reed-Sternberg cells) (100%, 33/33) (Clin Cancer Res 2008;14:7763, Blood 1985;66:848)
- T cell lymphomas
- Peripheral T cell lymphoma (85%) (Histopathology 2022;81:272)
- Mycosis fungoides (95%) (Blood Adv 2022;6:2290)
- Primary cutaneous anaplastic large cell lymphoma (100%) (Blood Adv 2022;6:2290)
- ALK positive / negative anaplastic large cell lymphoma (78% / 50%) (Blood Adv 2022;6:2290)
- Adult T cell leukemia / lymphoma (J Virol 2008;82:3843)
- Acute myeloid leukemia (86 - 100%) (Cancer Cell 2017;32:506, J Exp Med 2017;214:359)
- EBV associated malignancies
- Nasopharyngeal carcinoma (88%, 16/18) (Am J Pathol 1995;14:1152)
- Carcinoma
- Clear cell renal cell carcinoma (64%, 46/72) (Cancer Res 2006;66:2328)
- Thymic carcinoma (88%, 7/8) (Am J Surg Pathol 2000;24:742)
- Pulmonary sarcomatoid carcinoma (Eur J Cancer 2022;169:106)
Negative staining
- Carcinoma (Br J Cancer 2010;103:676)
- Lung (10%, 17/172)
- Breast (2%, 5/204)
- Pancreatic (25%, 35/140)
- Ovarian (15%, 37/241)
- Colon (9%, 17/194)
- Thymoma (0%) (Front Oncol 2022;11:808396)
- Thymic neuroendocrine tumor (0%) (Front Oncol 2022;11:808396)
- Osteosarcoma (19%, 16/83) (Cancer Cell Int 2015;15:31)
- Papillary renal cell carcinoma (40%) (Cancer Res 2006;66:2328)
- Mesothelioma (20%, 34/138) (J Pathol 2020;250:205)
- Melanoma (16%, 15/96) (Br J Cancer 2010;103:676)
- Glioblastoma (10 - 42%) (Cancer Res 2002;62:2592, Br J Cancer 2010;103:676)
- Multiple myeloma (42%, 13/31) (Clin Cancer Res 2008;14:7763)
Board review style question #1
Which of the following statements about CD70 is true?
- CD70 binds to CD28
- CD70 is negative in B cell lymphomas
- It is a sensitive and specific marker for multiple myeloma
- It is transiently expressed by activated immune cells
Board review style answer #1
D. CD70 is transiently expressed by activated immune cells. CD70 is the ligand to CD27. It is expressed in a majority of B and T cell lymphomas and is usually negative in plasma cell neoplasms.
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Reference: CD70
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