Tumor-infiltrating HLA-matched CD4+ T cells retargeted against Hodgkin and Reed-Sternberg cells

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...

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Bibliographic Details
Published in:	Oncoimmunology Vol. 5; no. 6; p. e1160186
Main Authors:	Rengstl, Benjamin, Schmid, Frederike, Weiser, Christian, Döring, Claudia, Heinrich, Tim, Warner, Kathrin, Becker, Petra S. A., Wistinghausen, Robin, Kameh-Var, Sima, Werling, Eva, Billmeier, Arne, Seidl, Christian, Hartmann, Sylvia, Abken, Hinrich, Küppers, Ralf, Hansmann, Martin-Leo, Newrzela, Sebastian
Format:	Journal Article
Language:	English
Published:	United States Taylor & Francis 02-06-2016
Subjects:	anti-tumor reaction CD4 chimeric antigen receptor (CAR) Hodgkin and Reed-Sternberg (HRS) cells Hodgkin lymphoma MHC-II compatible donors Original Research T cells chimeric antigen receptor (CAR) anti-tumor reaction Hodgkin and Reed-Sternberg (HRS) cells CD4+ T cells MHC-II compatible donors Hodgkin lymphoma
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Supplemental data for this article can be accessed on the publisher's website. M. -L. H. and S. N. contributed equally and share last authorship.
ISSN:	2162-4011 2162-402X 2162-402X
DOI:	10.1080/2162402X.2016.1160186