Expression of the immune checkpoint receptor TIGIT in Hodgkin's lymphoma

TY - JOUR

T1 - Expression of the immune checkpoint receptor TIGIT in Hodgkin's lymphoma

AU - Li, Wenchao

AU - Blessin, Niclas C

AU - Simon, Ronald

AU - Kluth, Martina

AU - Fischer, Kristine

AU - Hube-Magg, Claudia

AU - Makrypidi-Fraune, Georgia

AU - Wellge, Björn

AU - Mandelkow, Tim

AU - Debatin, Nicolaus F

AU - Pott, Laura

AU - Höflmayer, Doris

AU - Lennartz, Maximilian

AU - Sauter, Guido

AU - Izbicki, Jakob R

AU - Minner, Sarah

AU - Büscheck, Franziska

AU - Uhlig, Ria

AU - Dum, David

AU - Krech, Till

AU - Luebke, Andreas M

AU - Wittmer, Corinna

AU - Jacobsen, Frank

AU - Burandt, Eike

AU - Steurer, Stefan

AU - Wilczak, Waldemar

AU - Hinsch, Andrea

PY - 2018/12/4

Y1 - 2018/12/4

N2 - Hodgkin's lymphoma (HL) is characterized by a high background of inflammatory cells which play an important role for the pathogenesis of the disease. T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory immune checkpoint receptor and a putative target for novel immunotherapies. To study patterns of TIGIT expression in the T cell background surrounding malignant cells including Hodgkin cells, Reed-Sternberg cells and histiocytic cells, a microenvironment (ME) tissue microarray (TMA) was constructed from tissue punches measuring 2 mm in diameter obtained from formalin-fixed tissue samples of Hodgkin's lymphoma lymph nodes (n = 40) and normal human tonsil (n = 2). The ME-TMA was stained by brightfield and fluorescence multiplex immunohistochemistry (IHC) to evaluate expression levels of TIGIT and PD-1 as well as standard lymphocyte markers (CD3, CD8, CD4, FOXP3) in the lymphocytic background. All analyzed cases of HL contained 9-99% (median: 86%) of TIGIT+ lymphoid cells. In general, TIGIT localized to the same cells as PD-1. Strikingly, expression levels of TIGIT and PD-1 were highly variable among the analyzed samples. Highest levels of TIGIT and PD-1 were found in one sample of nodular lymphocytic-predominant HL (NLPHL). In conclusion, TIGIT expression is highly variable between patients with Hodgkin's lymphoma. Our results encourage further studies evaluating the role of TIGIT as a target for immunotherapies in Hodgkin's lymphoma.

AB - Hodgkin's lymphoma (HL) is characterized by a high background of inflammatory cells which play an important role for the pathogenesis of the disease. T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory immune checkpoint receptor and a putative target for novel immunotherapies. To study patterns of TIGIT expression in the T cell background surrounding malignant cells including Hodgkin cells, Reed-Sternberg cells and histiocytic cells, a microenvironment (ME) tissue microarray (TMA) was constructed from tissue punches measuring 2 mm in diameter obtained from formalin-fixed tissue samples of Hodgkin's lymphoma lymph nodes (n = 40) and normal human tonsil (n = 2). The ME-TMA was stained by brightfield and fluorescence multiplex immunohistochemistry (IHC) to evaluate expression levels of TIGIT and PD-1 as well as standard lymphocyte markers (CD3, CD8, CD4, FOXP3) in the lymphocytic background. All analyzed cases of HL contained 9-99% (median: 86%) of TIGIT+ lymphoid cells. In general, TIGIT localized to the same cells as PD-1. Strikingly, expression levels of TIGIT and PD-1 were highly variable among the analyzed samples. Highest levels of TIGIT and PD-1 were found in one sample of nodular lymphocytic-predominant HL (NLPHL). In conclusion, TIGIT expression is highly variable between patients with Hodgkin's lymphoma. Our results encourage further studies evaluating the role of TIGIT as a target for immunotherapies in Hodgkin's lymphoma.

KW - Journal Article

U2 - 10.1186/s12885-018-5111-1

DO - 10.1186/s12885-018-5111-1

M3 - SCORING: Journal article

C2 - 30514251

VL - 18

SP - 1209

JO - BMC CANCER

JF - BMC CANCER

SN - 1471-2407

IS - 1

ER -