Rengstl, Benjamin, Schmid, Frederike, Weiser, Christian, Doering, Claudia, Heinrich, Tim, Warner, Kathrin, Becker, Petra S. A., Wistinghausen, Robin, Kameh-Var, Sima, Werling, Eva, Billmeier, Arne, Seidl, Christian, Hartmann, Sylvia, Abken, Hinrich, Kueppers, Ralf, Hansmann, Martin-Leo and Newrzela, Sebastian (2016). Tumor-infiltrating HLA-matched CD4(+) T cells retargeted against Hodgkin and Reed-Sternberg cells. OncoImmunology, 5 (6). PHILADELPHIA: TAYLOR & FRANCIS INC. ISSN 2162-402X

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Abstract

Hodgkin lymphoma (HL) presents with a unique histologic pattern. Pathognomonic Hodgkin and Reed-Sternberg (HRS) cells usually account for less than 1% of the tumor and are embedded in a reactive infiltrate mainly comprised of CD4(+) T cells. HRS cells induce an immunosuppressive microenvironment and thereby escape antitumor immunity. To investigate the impact of interactions between HRS cells and T cells, we performed long-term co-culture studies that were further translated into a xenograft model. Surprisingly, we revealed a strong antitumor potential of allogeneic CD4(+) T cells against HL cell lines. HRS and CD4(+) T cells interact by adhesion complexes similar to immunological synapses. Tumor-cell killing was likely based on the recognition of allogeneic major histocompatibility complex class II (MHC-II) receptor, while CD4(+) T cells from MHC-II compatible donors did not develop any antitumor potential in case of HL cell line L428. However, gene expression profiling (GEP) of co-cultured HRS cells as well as tumor infiltration of matched CD4(+) T cells indicated cellular interactions. Moreover, matched CD4(+) T cells could be activated to kill CD30(+) HRS cells when redirected with a CD30-specific chimeric antigen receptor. Our work gives novel insights into the crosstalk between HRS and CD4(+) T cells, suggesting the latter as potent effector cells in the adoptive cell therapy of HL.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Rengstl, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmid, FrederikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weiser, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doering, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinrich, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Warner, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, Petra S. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wistinghausen, RobinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kameh-Var, SimaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Werling, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Billmeier, ArneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seidl, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmann, SylviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abken, HinrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kueppers, RalfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hansmann, Martin-LeoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Newrzela, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-289649
DOI: 10.1080/2162402X.2016.1160186
Journal or Publication Title: OncoImmunology
Volume: 5
Number: 6
Date: 2016
Publisher: TAYLOR & FRANCIS INC
Place of Publication: PHILADELPHIA
ISSN: 2162-402X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MHC CLASS-II; BISPECIFIC MONOCLONAL-ANTIBODIES; LYMPH-NODES; DISEASE; LYMPHOCYTES; EXPRESSION; RECEPTOR; BIOLOGY; RECRUITMENT; MODELMultiple languages
Oncology; ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/28964

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