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TIGIT EXPRESSION AND ITS SCORING SYSTEM IN CLASSIC HODGKIN LYMPHOMA: A NOVEL THERAPEUTIC TARGET?
Author(s): ,
Ombretta Annibali
Affiliations:
Unit of Hematology, Stem Cell Transplantation, Transfusion Medicine and Cellular Therapy, Department of Medicine,UNIVERSITÀ CAMPUS BIO-MEDICO ROMA,Roma,Italy
,
Antonella Bianchi
Affiliations:
UNIVERSITÀ CAMPUS BIO-MEDICO ROMA,Roma,Italy
,
Alba Grifoni
Affiliations:
La Jolla Institute for Allergy and Immunology,La Jolla,United States
,
Valeria Tomarchio
Affiliations:
Unit of Hematology, Stem Cell Transplantation, Transfusion Medicine and Cellular Therapy, Department of Medicine,UNIVERSITÀ CAMPUS BIO-MEDICO ROMA,Roma,Italy
,
Maria Antonietta Tafuri
Affiliations:
Unit of Hematology, Stem Cell Transplantation, Transfusion Medicine and Cellular Therapy, Department of Medicine,UNIVERSITÀ CAMPUS BIO-MEDICO ROMA,Roma,Italy
,
Martina Verri
Affiliations:
UNIVERSITÀ CAMPUS BIO-MEDICO ROMA,Roma,Italy
,
Giuseppe Avvisati
Affiliations:
Unit of Hematology, Stem Cell Transplantation, Transfusion Medicine and Cellular Therapy, Department of Medicine,UNIVERSITÀ CAMPUS BIO-MEDICO ROMA,Roma,Italy
Anna Crescenzi
Affiliations:
UNIVERSITÀ CAMPUS BIO-MEDICO ROMA,Roma,Italy
EHA Library. Annibali O. 06/09/21; 325625; EP867
Dr. Ombretta Annibali
Dr. Ombretta Annibali
Contributions
Abstract
Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP867

Type: E-Poster Presentation

Session title: Lymphoma Biology & Translational Research

Background
Clinical use of immune-checkpoints inhibitors (anti PD-1/PD-L1) resulted very effective for the treatment of relapsed/refractory classic Hodgkin Lymphoma (CHL). Recently, T cell Ig and ITIM domains (TIGIT) has been recognized as an immune checkpoint receptor able to negatively regulate T cell functions. 

Aims

Herein, we investigated the expression of TIGIT in CHL microenvironment in order to find a potential new target for inhibitor therapy.

Methods

TIGIT, PD-1 and PD-L1 expression was evaluated in 34 consecutive patients with CHL. In agreement with the evaluation model for immunohistochemical expression of PD-L1 in tumors, we proposed a scoring system for TIGIT immunohistochemistry in CHL; moreover, we compared TIGIT results with PD-1 and PD-L1 expression to obtain a complete assessment of the immunomodulation of Hodgkin lymphoma microenvironment.

Results

TIGIT expression in T lymphocytes surrounding Hodgkin Reed-Sternberg (HRS) cells was observed in 19/34 patients (56%), of which 11 (58%) had advanced stages. In 16/19 (84%) cases, TIGIT+ peritumoral T lymphocytes showed also PD-1 expression. All 15 TIGIT- patients had PD-L1 expression in HRS cells (100%) while among 19 TIGIT+ patients, 11 (58%) were PD-L1+ and 8 (42%) were PD-L1-. Using a new scoring system for TIGIT immunoreactivity, all TIGIT+ cases with higher score (4/19) were PD-L1-. Our results confirm co-expression of TIGIT and PD-1 in peritumoral T lymphocytes. Of relevance, we demonstrated a mutually exclusive expression of TIGIT and PD-L1 using new TIGIT scoring system able to identify this immunocheckpoints’ modulation.

Conclusion
In conclusion, our preliminary results in Hodgkin lymphoma, demonstrated a mutually exclusive expression of TIGIT in peritumoral lymphocytes and PD-L1 in HRS cells, with an overlap in cases with low level of TIGIT reactivity. The new TIGIT scoring system is able to identify such modulation of these immunocheckpoints. These results pave the way to new therapeutic strategies for relapsed/refractory CHL

Keyword(s): Hodgkin's lymphoma

Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP867

Type: E-Poster Presentation

Session title: Lymphoma Biology & Translational Research

Background
Clinical use of immune-checkpoints inhibitors (anti PD-1/PD-L1) resulted very effective for the treatment of relapsed/refractory classic Hodgkin Lymphoma (CHL). Recently, T cell Ig and ITIM domains (TIGIT) has been recognized as an immune checkpoint receptor able to negatively regulate T cell functions. 

Aims

Herein, we investigated the expression of TIGIT in CHL microenvironment in order to find a potential new target for inhibitor therapy.

Methods

TIGIT, PD-1 and PD-L1 expression was evaluated in 34 consecutive patients with CHL. In agreement with the evaluation model for immunohistochemical expression of PD-L1 in tumors, we proposed a scoring system for TIGIT immunohistochemistry in CHL; moreover, we compared TIGIT results with PD-1 and PD-L1 expression to obtain a complete assessment of the immunomodulation of Hodgkin lymphoma microenvironment.

Results

TIGIT expression in T lymphocytes surrounding Hodgkin Reed-Sternberg (HRS) cells was observed in 19/34 patients (56%), of which 11 (58%) had advanced stages. In 16/19 (84%) cases, TIGIT+ peritumoral T lymphocytes showed also PD-1 expression. All 15 TIGIT- patients had PD-L1 expression in HRS cells (100%) while among 19 TIGIT+ patients, 11 (58%) were PD-L1+ and 8 (42%) were PD-L1-. Using a new scoring system for TIGIT immunoreactivity, all TIGIT+ cases with higher score (4/19) were PD-L1-. Our results confirm co-expression of TIGIT and PD-1 in peritumoral T lymphocytes. Of relevance, we demonstrated a mutually exclusive expression of TIGIT and PD-L1 using new TIGIT scoring system able to identify this immunocheckpoints’ modulation.

Conclusion
In conclusion, our preliminary results in Hodgkin lymphoma, demonstrated a mutually exclusive expression of TIGIT in peritumoral lymphocytes and PD-L1 in HRS cells, with an overlap in cases with low level of TIGIT reactivity. The new TIGIT scoring system is able to identify such modulation of these immunocheckpoints. These results pave the way to new therapeutic strategies for relapsed/refractory CHL

Keyword(s): Hodgkin's lymphoma

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