Unknown

Dataset Information

0

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


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.

SUBMITTER: Rengstl B 

PROVIDER: S-EPMC4938355 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 mod  ...[more]

Similar Datasets

2016-11-29 | GSE75267 | GEO
| S-EPMC7760963 | biostudies-literature
| S-EPMC21471 | biostudies-literature
| S-EPMC11369618 | biostudies-literature
| S-EPMC2211891 | biostudies-literature
| S-EPMC6162537 | biostudies-literature
| S-EPMC6768943 | biostudies-literature
| S-EPMC6963251 | biostudies-literature
| S-EPMC3870723 | biostudies-literature
| S-EPMC151925 | biostudies-literature