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- El-Galaly, Tarec Christoffer, et al.
(författare)
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Late relapses in Hodgkin lymphoma - should we search for the needle in the haystack?
- 2022
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Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 198:1, s. 11-13
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Hodgkin lymphoma is among the most curable cancers. For patients in remission for 24 months, residual lifetime becomes close to that of the background population. However, late relapses can occur after several years and, as shown by Andersen et al., the outcomes are not always good.
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| 5. |
- Glimelius, Ingrid, 1975-
(författare)
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Hodgkin Lymphoma – an Interplay Between Tumour Cell and Microenvironment
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hodgkin lymphoma (HL) is a malignant disorder characterised by few tumour cells surrounded by a massive infiltrate of inflammatory cells, fibrosis, and microvessels. Therefore, it is a good model in which to study the interplay between tumour cells and the microenvironment. In a population-based series, stage IIB had poor prognosis, equivalent to the most advanced stage (stage IV). The most prominent negative prognostic factor was tumour bulk in the mediastinum (often large fibrotic tumours). The tumour cells expressed interleukin-9 (IL-9) in their cytoplasm in half of the cases. These cases had an over representation of nodular sclerosis histology (characterised by fibrotic bands) and infiltration of eosinophils and mast cells in the tumours. Despite this, IL-9 expression was not a negative prognostic factor. A role of inflammatory cells is to contribute to angiogenesis. Yet, a correlation between high microvessel count and high mast cell number in HL tumours was not identified, in contrast to other lymphomas. However, a correlation to poor prognosis was seen for cases with high microvessel count. Eosinophils contain eosinophil cationic protein (ECP). ECP was cytotoxic to cells from two HL cell lines of B-cell origin and one HL line of T-cell origin. At high concentrations, the cytotoxic effect was not as pronounced for the line of T-cell origin. If the in vitro cell lines are representative of HL in vivo, eosinophils may have different roles in different HL tumours. In addition to the effect from tumour cells, host-related factors contribute to the inflammatory infiltrate in HL. A history of asthma and hives, and carrying the ECP434GG genotype were associated with elevated numbers of eosinophils, whereas, history of tobacco smoking was associated with lower numbers. HL is a complex tumour consisting of recruited and subverted normal cells, fibrosis and angiogenesis: these constitute the microenvironment, which likely supports tumour cell growth, and differs between patients.
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| 6. |
- Hollander, Peter
(författare)
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Epidemiology and prognosis in classical Hodgkin lymphoma
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Classical Hodgkin lymphoma (HL) is a B cell derived neoplasm with an overall good prognosis. Its etiology and pathogenesis are largely unknown. The tumor microenvironment consists of sparse malignant cells and abundant leukocytes. In paper I we found that patients with rheumatoid arthritis (RA) had an increased risk of developing HL, especially patients with proxies of more severe RA. In addition, patients with RA had an especially increased risk of developing Epstein-Barr virus positive HL. These findings indicate that patients exposed to chronic inflammation have an increased risk of developing HL. We further studied the inflammatory milieu in the microenvironment of HL in paper II by investigating different leukocytes with immunohistochemical markers on diagnostic HL biopsies. We demonstrated that an anergic immune signature with a high amount of immune suppressive regulatory T lymphocytes was associated with inferior time to progression in an age-adjusted analysis. Another mechanism utilized by malignant cells and leukocytes to induce a suppressed antitumor immune response is to upregulate expression of programmed death ligands 1 and 2 (PD-L1 and PD-L2), that induces apoptosis in tumor killing leukocytes by binding to programmed death receptor 1 (PD-1). In paper III, we investigated the prognostic impact of PD-1, PD-L1 and PD-L2 in the tumor microenvironment of diagnostic HL biopsies with immunohistochemistry. We found that high proportions of PD-1+ and PD-L1+ leukocytes were associated with worse outcome in fully adjusted multivariate analyses. However, both PD-1 and PD-L1 are expressed to variable degrees in malignancies. Therefore, in paper IV we wanted to determine how expression of PD-1 and PD-L1 changes in repeated biopsies from both untreated and treated patients with relapsed HL. There were increased proportions of PD-1+ and PD-L1+ leukocytes, and PD-L1+ tumor cells in the relapse biopsies compared to the primary biopsies. These findings indicate that the PD-1 pathway is upregulated due to primary treatment, longer disease duration or altered conditions in the microenvironment at relapse.
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| 8. |
- Hollander, Peter, et al.
(författare)
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PD-1 and PD-L1 are upregulated in paired consecutive biopsies with classical Hodgkin lymphoma
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: High proportions of programmed death receptor 1 (PD-1) and its ligand (PD-L1) in the microenvironment of primary classical Hodgkin lymphoma (cHL) are associated with inferior outcome. However, it is unclear how expression alter during disease progression and if treatment and a subsequent relapse affect their expression. Our aim was to study the heterogeneity of PD-1 and PD-L1 in paired biopsies from untreated and treated cHL patientsPatients and methods: Patients with multiple biopsies with cHL were identified from three Swedish pathology departments. Eleven patients had a paired diagnostic cHL biopsy and a previous benign lymph node biopsy, which during our review were reclassified as cHL, designated as the untreated group. Thirty patients had a paired primary and a relapse biopsy, designated as the treated group. Cases were immunostained to detect PD-1+ and PD-L1+ leukocytes, and PD-L1+ Hodgkin and Reed-Sternberg (HRS) cells. Differences in expression between biopsies were tested using Wilcoxon signed rank test.Results: In the untreated group, 8 of 11 cases (73%) showed an increased proportion of PD-L1+ leukocytes in biopsy 2 compared to biopsy 1, while none of the markers were statistically significantly different when biopsy 1 and 2 were compared. In the treated group, 19 of 30 (63%), 22 of 30 (73%), and 18 of 30 (60%) cases showed increased proportions of PD-1+ leukocytes, PD-L1+ leukocytes and PD-L1+ HRS cells, respectively. When the primary and the relapse biopsies were compared, PD-1+ leukocytes (p=0.04), PD-L1+ leukocytes (p=0.005) and PD-L1+ HRS cells (p=0.009) were statistically significantly different. Conclusion: Our findings indicate that PD-1 and PD-L1 increase both due to longer disease duration and following treatment in relapsed cHL.
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