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Intra-tumoral and peripheral blood TIGIT and PD-1 as immune biomarkers in nodular lymphocyte predominant Hodgkin lymphoma.
Gunawardana, Jay; Law, Soi C; Sabdia, Muhammed B; Fennell, Éanna; Hennessy, Aoife; Leahy, Ciara I; Murray, Paul G; Bednarska, Karolina; Brosda, Sandra; Trotman, Judith; Berkahn, Leanne; Zaharia, Andreea; Birch, Simone; Burgess, Melinda; Talaulikar, Dipti; Lee, Justina N; Jude, Emily; Hawkes, Eliza A; Jain, Sanjiv; Nath, Karthik; Snell, Cameron; Swain, Fiona; Tobin, Joshua W D; Keane, Colm; Shanavas, Mohamed; Blyth, Emily; Steidl, Christian; Savage, Kerry; Farinha, Pedro; Boyle, Merrill; Meissner, Barbara; Green, Michael R; Vega, Francisco; Gandhi, Maher K.
Afiliação
  • Gunawardana J; Blood Cancer Research Group, Mater Research, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia.
  • Law SC; Blood Cancer Research Group, Mater Research, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia.
  • Sabdia MB; Blood Cancer Research Group, Mater Research, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia.
  • Fennell É; School of Medicine, Limerick Digital Cancer Research Centre, Health Research Institute and Bernal Institute, University of Limerick, Limerick, Ireland.
  • Hennessy A; School of Medicine, Limerick Digital Cancer Research Centre, Health Research Institute and Bernal Institute, University of Limerick, Limerick, Ireland.
  • Leahy CI; School of Medicine, Limerick Digital Cancer Research Centre, Health Research Institute and Bernal Institute, University of Limerick, Limerick, Ireland.
  • Murray PG; School of Medicine, Limerick Digital Cancer Research Centre, Health Research Institute and Bernal Institute, University of Limerick, Limerick, Ireland.
  • Bednarska K; Royal College of Surgeons Ireland, Adliya, Bahrain.
  • Brosda S; Blood Cancer Research Group, Mater Research, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia.
  • Trotman J; Frazer Institute, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia.
  • Berkahn L; Concord Repatriation General Hospital, University of Sydney, Sydney, New South Wales, Australia.
  • Zaharia A; Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.
  • Birch S; Department of Haematology, Auckland City Hospital, Auckland, New Zealand.
  • Burgess M; Blood Cancer Research Group, Mater Research, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia.
  • Talaulikar D; Princess Alexandra Hospital, Brisbane, Queensland, Australia.
  • Lee JN; School of Medicine, Limerick Digital Cancer Research Centre, Health Research Institute and Bernal Institute, University of Limerick, Limerick, Ireland.
  • Jude E; Princess Alexandra Hospital, Brisbane, Queensland, Australia.
  • Hawkes EA; Haematology Translational Research Unit, ACT Pathology, Canberra Health Services, Canberra, Australian Capital Territory, Australia.
  • Jain S; College of Health and Medicine, Australian National University, Canberra, Australian Capital Territory, Australia.
  • Nath K; Blood Cancer Research Group, Mater Research, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia.
  • Snell C; Austin Health, Heidelberg, Victoria, Australia.
  • Swain F; Olivia Newton John Cancer Research and Wellness Centre, Austin Health, Melbourne, Victoria, Australia.
  • Tobin JWD; Transfusion Research Unit, School of Public Health and Preventative Medicine, Monash University, Melbourne, Victoria, Australia.
  • Keane C; Anatomical Pathology Department, The Canberra Hospital, Canberra, Australian Capital Territory, Australia.
  • Shanavas M; Blood Cancer Research Group, Mater Research, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia.
  • Blyth E; Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Steidl C; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Savage K; Mater Pathology, Brisbane, Queensland, Australia.
  • Farinha P; Royal College of Surgeons Ireland, Adliya, Bahrain.
  • Boyle M; Princess Alexandra Hospital, Brisbane, Queensland, Australia.
  • Meissner B; Blood Cancer Research Group, Mater Research, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia.
  • Green MR; Princess Alexandra Hospital, Brisbane, Queensland, Australia.
  • Vega F; Frazer Institute, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia.
  • Gandhi MK; Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Am J Hematol ; 99(11): 2096-2107, 2024 Nov.
Article em En | MEDLINE | ID: mdl-39152767
ABSTRACT
In classical Hodgkin lymphoma (cHL), responsiveness to immune-checkpoint blockade (ICB) is associated with specific tumor microenvironment (TME) and peripheral blood features. The role of ICB in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is not established. To gain insights into its potential in NLPHL, we compared TME and peripheral blood signatures between HLs using an integrative multiomic analysis. A discovery/validation approach in 121 NLPHL and 114 cHL patients highlighted >2-fold enrichment in programmed cell death-1 (PD-1) and T-cell Ig and ITIM domain (TIGIT) gene expression for NLPHL versus cHL. Multiplex imaging showed marked increase in intra-tumoral protein expression of PD-1+ (and/or TIGIT+) CD4+ T-cells and PD-1+CD8+ T-cells in NLPHL compared to cHL. This included T-cells that rosetted with lymphocyte predominant (LP) and Hodgkin Reed-Sternberg (HRS) cells. In NLPHL, intra-tumoral PD-1+CD4+ T-cells frequently expressed TCF-1, a marker of heightened T-cell response to ICB. The peripheral blood signatures between HLs were also distinct, with higher levels of PD-1+TIGIT+ in TH1, TH2, and regulatory CD4+ T-cells in NLPHL versus cHL. Circulating PD-1+CD4+ had high levels of TCF-1. Notably, in both lymphomas, highly expanded populations of clonal TIGIT+PD-1+CD4+ and TIGIT+PD-1+CD8+ T-cells in the blood were also present in the TME, indicating that immune-checkpoint expressing T-cells circulated between intra-tumoral and blood compartments. In in vitro assays, ICB was capable of reducing rosette formation around LP and HRS cells, suggesting that disruption of rosetting may be a mechanism of action of ICB in HL. Overall, results indicate that further evaluation of ICB is warranted in NLPHL.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Hodgkin / Receptores Imunológicos / Biomarcadores Tumorais / Microambiente Tumoral / Receptor de Morte Celular Programada 1 Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Hodgkin / Receptores Imunológicos / Biomarcadores Tumorais / Microambiente Tumoral / Receptor de Morte Celular Programada 1 Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article