Classical Hodgkin’s Lymphoma in the Era of Immune Checkpoint Inhibition

Re, Vallì De; Caggiari, Laura; Repetto, Ombretta; Mussolin, Lara; Mascarin, Maurizio

doi:10.3390/jcm8101596

Cited by 18 publications

(23 citation statements)

References 122 publications

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“…HL cells use multiple mechanisms for immune escape and self-destruction avoidance [39][40][41]. In particular, in adult classic HL, immune escape is mediated by overexpression of programmed cell death 1 ligand 1 (PD-L1) on the surface of Hodgkin-Reed-Sternberg cells (reviewed in [39]). Overexpression in turn antagonizes the activity of PD-1-positive T cells and leads to tumor evasion of destruction by the immune system [42].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma

Repetto

Mussolin

et al. 2020

IJMS

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The identification of circulating proteins associated with relapse in pediatric Hodgkin lymphoma (HL) may help develop predictive biomarkers. We previously identified a set of predictive biomarkers by difference gel electrophoresis. Here we used label-free quantitative liquid chromatography-mass spectrometry (LC-MS/MS) on plasma collected at diagnosis from 12 children (age 12–16 years) with nodular sclerosis HL, including six in whom the disease relapsed within 5 years of treatment in the LH2004 trial. Plasma proteins were pooled in groups of three, separately for non-relapsing and relapsing HL, and differentially abundant proteins between the two disease states were identified by LC-MS/MS in an explorative and validation design. Proteins with a fold change in abundance >1.2 or ≤0.8 were considered “differentially abundant”. LC-MS/MS identified 60 and 32 proteins that were more abundant in non-relapsing and relapsing HL plasma, respectively, in the explorative phase; these numbers were 39 and 34 in the validation phase. In both analyses, 11 proteins were more abundant in non-relapsing HL (e.g., angiotensinogen, serum paraoxonase/arylesterase 1, transthyretin), including two previously identified by difference gel electrophoresis (antithrombin III and α-1-antitrypsin); seven proteins were more abundant in relapsing HL (e.g., fibronectin and thrombospondin-1), including two previously identified proteins (fibrinogen β and γ chains). The differentially abundant proteins participated in numerous biological processes, which were manually grouped into 10 biological classes and 11 biological regulatory subclasses. The biological class Lipid metabolism, and its regulatory subclass, included angiotensinogen and serum paraoxonase/arylesterase 1 (more abundant in non-relapsing HL). The biological classes Immune system and Cell and extracellular matrix architecture included fibronectin and thrombospondin-1 (more abundant in relapsing HL). These findings deepen our understanding of the molecular scenario underlying responses to therapy and provide new evidence about these proteins as possible biomarkers of relapse in pediatric HL.

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Section: Discussionmentioning

confidence: 99%

Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma

Repetto

Mussolin

et al. 2020

IJMS

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“…They are a major immune component of the tumor microenvironment and a good prognostic biomarker for disease-free survival and overall survival. TAMs are involved in various aspects of tumor progression including aberrant cytokine secretion, a driver of immune checkpoint blockade particularly important in Hodgkin lymphoma where the PD-L1 gene is amplified in tumor cells [29]. TAMs are also important in tumor matrix remodeling, angiogenesis, and resistance to treatment [30].…”

Section: Bart Mirnas In Hodgkin Lymphomamentioning

confidence: 99%

Epstein-Barr virus BART microRNAs in EBV- associated Hodgkin lymphoma and gastric cancer

Caggiari

Zorzi

et al. 2020

Infect Agents Cancer

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Background: EBV produces miRNAs with important functions in cancer growth, tumor invasion and host immune surveillance. The discovery of EBV miR-BARTs is recent, and most of their functions are still unknown. Nonetheless, some new studies underline their key roles in EBV-associated malignancies. Main body: In EBV-associated tumors, the expression profile of miR-BARTs varies according to the cell type, autophagic process and signals received from the tumor microenvironment. By the same way of interest is the interaction between tumor cells and the tumor environment by the release of selected EBV miR-BARTs in addition to the tumor proteins trough tumor exosomes. Conclusion: In this review, we discuss new findings regarding EBV miR-BARTs in Hodgkin lymphoma and gastric cancer. The recent discovery that miRNAs are released by exosomes, including miR-BARTs, highlights the importance of tumor and microenvironment interplay with more specific effects on the host immune response.

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“…Interestingly, both studies demonstrated that RT results in increased PD-L1 expression in vivo through interferon gamma production by T cells and that this appears to be an adaptive resistance pathway [ 10 ] that can be overcome by PD-L1-blockade [ 76 ]. Haematological malignancies such as Hodgkin lymphoma also show upregulation of PD-L1/PD-1 after chemotherapy/radiotherapy [ 77 ] and are known to be highly responsive to PD-1 blockade [ 78 ], and RT in combination with PD-1 blockade can induce abscopal responses [ 79 ]. The Pacific study showed that the addition of durvalumab (anti PD-L1) after consolidated chemoradiotherapy (CRT) enhanced both progression free survival (PFS) and overall survival (OS) of phase III unresectable non-small-cell lung carcinoma (NSCLC) patients; subgroup analysis showed that survival benefit was achieved in both PD-L1 positive and negative patients [ 76 ].…”

Section: Biomarkersmentioning

confidence: 99%

Understanding the Effects of Radiotherapy on the Tumour Immune Microenvironment to Identify Potential Prognostic and Predictive Biomarkers of Radiotherapy Response

Cheng

Cheadle

Illidge

2020

Cancers

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Radiotherapy (RT) is a highly effective anti-cancer treatment. Immunotherapy using immune checkpoint blockade (ICI) has emerged as a new and robust pillar in cancer therapy; however, the response rate to single agent ICI is low whilst toxicity remains. Radiotherapy has been shown to have local and systemic immunomodulatory effects. Therefore, combining RT and immunotherapy is a rational approach to enhance anti-tumour immune responses. However, the immunomodulatory effects of RT can be both immunostimulatory or immunosuppressive and may be different across different tumour types and patients. Therefore, there is an urgent medical need to establish biomarkers to guide clinical decision making in predicting responses or in patient selection for RT-based combination treatments. In this review, we summarize the immunological effects of RT on the tumour microenvironment and emerging biomarkers to help better understand the implications of these immunological changes, and we provide new insights into the potential for combination therapies with RT and immunotherapy.

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Classical Hodgkin’s Lymphoma in the Era of Immune Checkpoint Inhibition

Cited by 18 publications

References 122 publications

Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma

Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma

Epstein-Barr virus BART microRNAs in EBV- associated Hodgkin lymphoma and gastric cancer

Understanding the Effects of Radiotherapy on the Tumour Immune Microenvironment to Identify Potential Prognostic and Predictive Biomarkers of Radiotherapy Response

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