A novel scoring system for TIGIT expression in classic Hodgkin lymphoma

Annibali, Ombretta; Bianchi, Antonella; Grifoni, Alba; Tomarchio, Valeria; Tafuri, Mariantonietta; Verri, Martina; Avvisati, Giuseppe; Crescenzi, Anna

doi:10.1038/s41598-021-86655-8

Cited by 15 publications

(15 citation statements)

References 18 publications

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“…In relapsed/refractory classic Hodgkin’s lymphoma, a TIGIT-mediated alternative system of immune escape was demonstrated to the classic PD-1/PD-L1 ( 141 ). TIGIT and PD-L1 were found to be mutually exclusively expressed and TIGIT + PD-1 + CD3 + CD4 + T cells surrounding Hodgkin Reed-Sternberg (HRS) cells were associated with advanced TNM stages ( 141 ).…”

Section: Tigit In Cancer Progressionmentioning

confidence: 99%

Update in TIGIT Immune-Checkpoint Role in Cancer

2022

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The in-depth characterization of cross-talk between tumor cells and T cells in solid and hematological malignancies will have to be considered to develop new therapeutical strategies concerning the reactivation and maintenance of patient-specific antitumor responses within the patient tumor microenvironment. Activation of immune cells depends on a delicate balance between activating and inhibitory signals mediated by different receptors. T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed by regulatory T cells (Tregs), activated T cells, and natural killer (NK) cells. TIGIT pathway regulates T cell-mediated tumor recognition in vivo and in vitro and represents an exciting target for checkpoint blockade immunotherapy. TIGIT blockade as monotherapy or in combination with other inhibitor receptors or drugs is emerging in clinical trials in patients with cancer. The purpose of this review is to update the role of TIGIT in cancer progression, looking at TIGIT pathways that are often upregulated in immune cells and at possible therapeutic strategies to avoid tumor aggressiveness, drug resistance, and treatment side effects. However, in the first part, we overviewed the role of immune checkpoints in immunoediting, the TIGIT structure and ligands, and summarized the key immune cells that express TIGIT.

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Section: Tigit In Cancer Progressionmentioning

confidence: 99%

Update in TIGIT Immune-Checkpoint Role in Cancer

2022

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“…This data is comparable to the other studies in which PD-1 expression was observed in less than 40% of cases (range 16–40%) [ 28 , 30 , 46 ]. TIM-3 expression was observed in 100% of adult cHL cases [ 47 ], LAG-3 expression was found in 63% of pediatric cases [ 48 ] and in 100% of adult cases [ 47 ], TIGIT expression ranged from 56% (cases where cells surrounded HRS) [ 49 ] to 100% [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies and reviews reported that increased numbers of PD-1-positive cells were associated with worse outcomes and shorter survival in cHL patients [ 28 , 30 , 53 , 54 , 55 , 56 ] while other researchers showed that PD-1 expression had no significant association with survival [ 57 , 58 ]. TIGIT status did not correlate with response to treatment [ 49 ]. LAG-3 expression was not associated with survival outcomes in pediatric cases [ 48 ] but had prognostic significance in adult patients [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Immunosuppressive Microenvironment and Efficacy of PD-1 Inhibitors in Relapsed/Refractory Classic Hodgkin Lymphoma: Checkpoint Molecules Landscape and Macrophage Populations

Gusak

Fedorova

Lepik

et al. 2021

Cancers

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To date, the impact of the tumor microenvironment on the prognosis of patients with classic Hodgkin lymphoma (cHL) during anti-PD-1 therapy has been studied insufficiently. This retrospective study included 61 primary samples of lymph nodes from patients who had relapsed/refractory (r/r) cHL and were treated with nivolumab. Repeated samples were obtained in 15 patients at relapse or disease progression after immunotherapy. Median follow-up was 55 (13–63) months. The best overall response rate and progression-free survival (PFS) were analyzed depending on the expression of CD68, CD163, PD-1, LAG-3, TIM-3, CTLA-4, TIGIT, CD163/c-maf in the tumor microenvironment in primary and sequential biopsies. The combination of CD163/c-maf antibodies was used for the identification of M2 macrophages (M2). A low number of macrophages in primary samples was associated with inferior PFS during nivolumab treatment (for CD163-positive cells p = 0.0086; for CD68-positive cells p = 0.037), while a low number of M2 with higher PFS (p = 0.014). Complete response was associated with a lower level of M2 (p = 0.011). In sequential samples (before and after nivolumab therapy) an increase in PD-1 (p = 0.011) and LAG-3 (p = 0.0045) and a depletion of CD68 (p = 0.057) and CD163 (p = 0.0049)-positive cells were observed. The study expands understanding of the cHL microenvironment structure and dynamics during nivolumab therapy in patients with r/r cHL.

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“…Therefore, clinical trials targeting LAG-3 (relatlimab, NCT02061761) or TIM-3 (BMS-986258, NCT03446040) alone or in combination with nivolumab in the treatment of r/r HL are completed, and results will be released soon. In addition, T-cell Ig and ITIM domains (TIGIT) are another immune checkpoint receptor that is found to be highly co-expressed with PD-1 in r/r cHL patients [116]. Therefore, co-inhibition of PD-1 and TIGIT could be a novel strategy for treating r/r cHL.…”

Section: Other Potential Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Immune Checkpoint Inhibitors in Hodgkin Lymphoma and Non-Hodgkin Lymphoma

Huang¹,

Huang²

2023

Immune Checkpoint Inhibitors - New Insights and Recent Progress

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Lymphoma, which mainly includes Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL), is the most common hematological malignance of the lymphoid tissues with significantly heterogeneous characteristics. Tumor immune disequilibrium is involved in tumor development and progression, evading tumor immunosurveillance and suppressing anti-tumor immune responses. The tumor microenvironment (TME) is a complex network that comprises stromal cells and extracellular matrix, playing important roles in the pathogenesis, progression, and drug resistance of lymphoma. Therefore, a promising therapeutic strategy for lymphoma is by targeting the TME to stimulate anticancer immunity either by enhancing the release of immunostimulatory molecules or by mediating immune cell populations. Notably, immune checkpoint therapy (ICT) can provide durable clinical responses and improve overall survival in HL and NHL. However, different subsets of patients with lymphoma have different responses to ICT. Thus, significant challenges remain, including understanding pathways of resistance, optimizing patient selection, improving the management of immune-related adverse events, and identifying rational therapeutic combinations. This will allow a better understanding of the potential applications of ICT in lymphoma, guiding decisions to develop novel combination strategies with maximum efficacy and minimal toxicities for patients.

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A novel scoring system for TIGIT expression in classic Hodgkin lymphoma

Cited by 15 publications

References 18 publications

Update in TIGIT Immune-Checkpoint Role in Cancer

Update in TIGIT Immune-Checkpoint Role in Cancer

Immunosuppressive Microenvironment and Efficacy of PD-1 Inhibitors in Relapsed/Refractory Classic Hodgkin Lymphoma: Checkpoint Molecules Landscape and Macrophage Populations

Immune Checkpoint Inhibitors in Hodgkin Lymphoma and Non-Hodgkin Lymphoma

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