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

Li, Wenchao; Blessin, Niclas C.; Simon, Ronald; Kluth, Martina; Fischer, Kristine; Hube‐Magg, Claudia; Makrypidi‐Fraune, Georgia; Wellge, Björn; Mandelkow, Tim; Debatin, Nicolaus F.; Pott, Laura; Höflmayer, Doris; Lennartz, Maximilian; Sauter, Guido; Izbicki, Jakob R.; Minner, Sarah; Büscheck, Franziska; Uhlig, Ria; Dum, David; Krech, Till; Luebke, Andreas M.; Wittmer, Corinna; Jacobsen, Frank; Burandt, Eike; Steurer, Stefan; Wilczak, Waldemar; Hinsch, Andrea

doi:10.1186/s12885-018-5111-1

Cited by 33 publications

(27 citation statements)

References 45 publications

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“…Our data confirm that TIGIT is frequently expressed in T lymphocytes within the tumor microenvironment of CHL 8 and TIGIT expression seems to be related to CD4+ activated T lymphocytes surrounding the malignant HRS cells. The immune-morphologically well-known rosettes of T lymphocytes surrounding the neoplastic cells 10 , demonstrated by the three-dimensional reconstruction using a confocal microscopy, reveal to have actually an immune-suppressive functional role.…”

Section: Discussionsupporting

confidence: 82%

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A novel scoring system for TIGIT expression in classic Hodgkin lymphoma

Annibali

Bianchi

Grifoni

et al. 2021

Sci Rep

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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. Herein, we investigated the expression of TIGIT in CHL microenvironment in order to find a potential new target for inhibitor therapy. TIGIT, PD-1 and PD-L1 expression was evaluated in 34 consecutive patients with CHL. 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. These results pave the way to new therapeutic strategies for relapsed/refractory CHL.

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Section: Discussionsupporting

confidence: 82%

“…Recently, TIGIT expression has been reported in CHL in lymphocytes surrounding HRS cells 8 . Although it was the first evidence of TIGIT expression in CHL, this result has not been correlated with other immunocheckpoints and a scoring system to grade TIGIT immunohistochemical expression has not been described.…”

Section: Introductionmentioning

confidence: 99%

A novel scoring system for TIGIT expression in classic Hodgkin lymphoma

Annibali

Bianchi

Grifoni

et al. 2021

Sci Rep

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“…Variable expression of PD-1 and TIGIT was observed on CD3 + T cells in patients with Hodgkin lymphoma, suggesting that TIGIT blockade alone or in combination with other drugs might be used as a potential therapeutic target. However, further evaluation is required (164). As PD-1 or TIM-3 are co-expressed by TIGIT-positive T cells, targeting TIGIT could be an additional mechanism to avert exhaustion of T cells in B-cell Non-Hodgkin Lymphoma (B-NHL) (155).…”

Section: Tigit and Cd96mentioning

confidence: 99%

NK Cell-Based Immune Checkpoint Inhibition

Arooj²,

2020

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Immunotherapy, with an increasing number of therapeutic dimensions, is becoming an important mode of treatment for cancer patients. The inhibition of immune checkpoints, which are the source of immune escape for various cancers, is one such immunotherapeutic dimension. It has mainly been aimed at T cells in the past, but NK cells are a newly emerging target. Simultaneously, the number of checkpoints identified has been increasing in recent times. In addition to the classical NK cell receptors KIRs, LIRs, and NKG2A, several other immune checkpoints have also been shown to cause dysfunction of NK cells in various cancers and chronic infections. These checkpoints include the revolutionized CTLA-4, PD-1, and recently identified B7-H3, as well as LAG-3, TIGIT & CD96, TIM-3, and the most recently acknowledged checkpoint-members of the Siglecs family (Siglec-7/9), CD200 and CD47. An interesting dimension of immune checkpoints is their candidacy for dual-checkpoint inhibition, resulting in therapeutic synergism. Furthermore, the combination of immune checkpoint inhibition with other NK cell cytotoxicity restoration strategies could also strengthen its efficacy as an antitumor therapy. Here, we have undertaken a comprehensive review of the literature to date regarding NK cell-based immune checkpoints.

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“…The most striking observation in our study was the high variability of the relative fraction of TIGIT + and PD-1 + lymphocytes in seminomas. We earlier reported a similar diversity of the relative role of TIGIT and PD-1 in a cohort of 40 Hodgkin's lymphomas (41). If it holds true that the different checkpoint receptors are so variably expressed in individual cancer patients, the analysis of the inflammatory cells may proof instrumental to select the optimal immune checkpoint inhibitor for a given patient.…”

Section: Discussionmentioning

confidence: 63%

Expression of the immune checkpoint receptor TIGIT in seminoma

et al. 2019

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A characteristic feature of testicular seminoma is the abundance of immune cells in the tumor microenvironment, raising the possibility that immune checkpoint inhibitors may serve as a therapeutic option in these types of tumors. T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory immune checkpoint receptor in analogy to PD-1, and drugs targeting TIGIT are currently being investigated in clinical trials. Little is known about the expression of these proteins in testicular seminomas. Therefore the present study performed immunohistochemical analysis to determine the relative abundance of TIGIT and PD-1 in relation to the total CD3 + immune cell infiltration in a tissue microarray (TMA) constructed from 78 seminoma patients. The fraction of TIGIT + and PD-1 + lymphocytes was highly variable in individual cancers and ranged from 2.3 to 69.4% (mean: 32.2±14.7%) for TIGIT and from 0.8 to 56.5% (mean: 21.6±13.2%) for PD-1. The same high degree of variability was also identified for the ratio of PD-1 to TIGIT positive cells, which varied from a dominance of TIGIT (PD-1: TIGIT ratio=0.02) in 74% of patients, to a predominance of PD-1 (PD-1: TIGIT ratio=12.5) in 23% of patients. In summary, the immune checkpoint receptors TIGIT and PD-1 are abundantly expressed in human seminomas. Once available, anti-TIGIT antibodies, possibly in combination with anti-PD-1 drugs, may be a reasonable therapeutic strategy for this type of cancer.

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

Cited by 33 publications

References 45 publications

A novel scoring system for TIGIT expression in classic Hodgkin lymphoma

A novel scoring system for TIGIT expression in classic Hodgkin lymphoma

NK Cell-Based Immune Checkpoint Inhibition

Expression of the immune checkpoint receptor TIGIT in seminoma

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