Intra-tumoral and peripheral blood TIGIT and PD-1 as immune biomarkers in nodular lymphocyte predominant Hodgkin lymphoma Journal Article
| Authors: | Gunawardana, J.; Law, S. C.; Sabdia, M. B.; Fennell, É; Hennessy, A.; Leahy, C. I.; Murray, P. G.; Bednarska, K.; Brosda, S.; Trotman, J.; Berkahn, L.; Zaharia, A.; Birch, S.; Burgess, M.; Talaulikar, D.; Lee, J. N.; Jude, E.; Hawkes, E. A.; Jain, S.; Nath, K.; Snell, C.; Swain, F.; Tobin, J. W. D.; Keane, C.; Shanavas, M.; Blyth, E.; Steidl, C.; Savage, K.; Farinha, P.; Boyle, M.; Meissner, B.; Green, M. R.; Vega, F.; Gandhi, M. K. |
| Article Title: | Intra-tumoral and peripheral blood TIGIT and PD-1 as immune biomarkers in nodular lymphocyte predominant Hodgkin lymphoma |
| 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. © 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC. |
| Keywords: | immunohistochemistry; adult; controlled study; human tissue; protein expression; aged; middle aged; unclassified drug; major clinical study; flow cytometry; transcription factor foxp3; cd8+ t lymphocyte; cd8-positive t-lymphocytes; biological marker; diagnostic procedure; gene expression; tumor marker; hodgkin disease; t lymphocyte receptor; blood; immunology; gamma interferon; diagnosis; cd4+ t lymphocyte; cd4-positive t-lymphocytes; immunophenotyping; rosette formation; tissue microarray; fluorescence activated cell sorting; lymphocyte function associated antigen 3; cd134 antigen; peripheral blood mononuclear cell; transcription factor 7; nodular lymphocyte predominant hodgkin lymphoma; receptors, immunologic; classical hodgkin lymphoma; reed sternberg cell; programmed death 1 ligand 1; programmed death 1 receptor; thymus and activation regulated chemokine; tumor microenvironment; immunoglobulin receptor; peptides and proteins; rna hybridization; cd36 antigen; humans; human; male; female; article; programmed death 1 ligand 2; differential gene expression; pdcd1 protein, human; programmed cell death 1 receptor; biomarkers, tumor; hepatitis a virus cellular receptor 2; tumor necrosis factor receptor superfamily member 8; multiomics; tigit protein, human; cxcl11 gene; tigit protein; cd155 protein; ctss protein; nlrc5 protein; hsd11b1 gene; multispectral microscopy |
| Journal Title: | American Journal of Hematology |
| Volume: | 99 |
| Issue: | 11 |
| ISSN: | 0361-8609 |
| Publisher: | John Wiley & Sons, Inc. |
| Date Published: | 2024-11-01 |
| Start Page: | 2096 |
| End Page: | 2107 |
| Language: | English |
| DOI: | 10.1002/ajh.27459 |
| PUBMED: | 39152767 |
| PROVIDER: | scopus |
| PMCID: | PMC11469944 |
| DOI/URL: | |
| Notes: | Source: Scopus |
