CD27 signaling increases the frequency of regulatory T cells and promotes tumor growth

Claus, Christina; Riether, Carsten; Schürch, Christian; Matter, Matthias S; Hilmenyuk, Tamara; Ochsenbein, Adrian (2012). CD27 signaling increases the frequency of regulatory T cells and promotes tumor growth. Cancer research, 72(14), pp. 3664-76. Birmingham, Ala.: American Association for Cancer Research AACR 10.1158/0008-5472.CAN-11-2791

[img] Text
Cancer Res-2012-Claus-3664-76.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (3MB) | Request a copy

Signaling of the TNF receptor superfamily member CD27 activates costimulatory pathways to elicit T- and B-cell responses. CD27 signaling is regulated by the expression of its ligand CD70 on subsets of dendritic cells and lymphocytes. Here, we analyzed the role of the CD27-CD70 interaction in the immunologic control of solid tumors in Cd27-deficient mice. In tumor-bearing wild-type mice, the CD27-CD70 interaction increased the frequency of regulatory T cells (Tregs), reduced tumor-specific T-cell responses, increased angiogenesis, and promoted tumor growth. CD27 signaling reduced apoptosis of Tregs in vivo and induced CD4(+) effector T cells (Teffs) to produce interleukin-2, a key survival factor for Tregs. Consequently, the frequency of Tregs and growth of solid tumors were reduced in Cd27-deficient mice or in wild-type mice treated with monoclonal antibody to block CD27 signaling. Our findings, therefore, provide a novel mechanism by which the adaptive immune system enhances tumor growth and may offer an attractive strategy to treat solid tumors.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Service Sector > Institute of Pathology > Autopsy
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Claus, Christina; Riether, Carsten; Schürch, Christian; Hilmenyuk, Tamara and Ochsenbein, Adrian

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0008-5472

Publisher:

American Association for Cancer Research AACR

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:33

Last Modified:

16 Jul 2015 08:22

Publisher DOI:

10.1158/0008-5472.CAN-11-2791

PubMed ID:

22628427

Web of Science ID:

000307353200023

BORIS DOI:

10.7892/boris.12777

URI:

https://boris.unibe.ch/id/eprint/12777 (FactScience: 219248)

Actions (login required)

Edit item Edit item
Provide Feedback