Adjuvant Dendritic Cell Vaccination in High-Risk Uveal Melanoma

Bol, Kalijn F.; Bosch, Thomas van den; Schreibelt, Gerty; Mensink, Hanneke W.; Keunen, J. E. E.; Kılıç, Emine; Japing, Wouter J.; Geul, Kaspar W.; Westdorp, Harm; Boudewijns, Steve; Croockewit, Sandra; Rossum, Michelle M. van; Goede, Anna L. de; Naus, Nicole; Graaf, Winette T.A. van der; Gerritsen, Winald R.; Klein, Annelies de; Punt, Cornelis J.A.; Figdor, Carl G.; Cohen, Victoria M L; Paridaens, Dion; Vries, I. Jolanda M. de

doi:10.1016/j.ophtha.2016.06.027

Cited by 43 publications

(27 citation statements)

References 5 publications

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“…DC vaccination achieved a 3-year OS of 79% and a median disease-free survival of 34.5 months. Similar to the study mentioned above, no grade 3 or 4 toxicities were observed, and the most common AEs were flu-like symptoms (21 patients, 91%) and erythema at the site of the DC injection (20 patients, 87%) [181]. Currently, a multicenter, open-label, randomized phase III trial investigating adjuvant DC vaccination versus observation only is ongoing (NCT01983748) [182].…”

Section: Making Cold Tumors Hot For Immune Cells: Considerations For mentioning

confidence: 59%

The Role of Immune Checkpoint Blockade in Uveal Melanoma

Wessely

Steeb

Erdmann

et al. 2020

IJMS

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Uveal melanoma (UM) represents the most common intraocular malignancy in adults and accounts for about 5% of all melanomas. Primary disease can be effectively controlled by several local therapy options, but UM has a high potential for metastatic spread, especially to the liver. Despite its clinical and genetic heterogeneity, therapy of metastatic UM has largely been adopted from cutaneous melanoma (CM) with discouraging results until now. The introduction of antibodies targeting CTLA-4 and PD-1 for immune checkpoint blockade (ICB) has revolutionized the field of cancer therapy and has achieved pioneering results in metastatic CM. Thus, expectations were high that patients with metastatic UM would also benefit from these new therapy options. This review provides a comprehensive and up-to-date overview on the role of ICB in UM. We give a summary of UM biology, its clinical features, and how it differs from CM. The results of several studies that have been investigating ICB in metastatic UM are presented. We discuss possible reasons for the lack of efficacy of ICB in UM compared to CM, highlight the pitfalls of ICB in this cancer entity, and explain why other immune-modulating therapies could still be an option for future UM therapies.

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Section: Making Cold Tumors Hot For Immune Cells: Considerations For mentioning

confidence: 59%

The Role of Immune Checkpoint Blockade in Uveal Melanoma

Wessely

Steeb

Erdmann

et al. 2020

IJMS

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“…However, UM cells can inhibit DC immunostimulatory function, and it would appear that DCs in the context of high tumour volume mUM are incapable of stimulating an effective immune response [ 40 ]. Hence, trials were established to treat high-risk UM patients (identified by monosomy 3 of the primary tumour) with DC vaccinations in an adjuvant setting after resection of the primary tumour [ 41 , 42 ]. A slight improvement in overall survival rates was achieved in patients with a detectable tumour antigen-specific immune response after DC vaccination.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Profiling Reveals New Insights into the Immune Microenvironment and Upregulation of Novel Biomarkers in Metastatic Uveal Melanoma

Krishna

Acha-Sagredo

Sabat-Pośpiech

et al. 2020

Cancers

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Metastatic uveal melanoma (mUM) to the liver is incurable. Transcriptome profiling of 40 formalin-fixed paraffin-embedded mUM liver resections and 6 control liver specimens was undertaken. mUMs were assessed for morphology, nuclear BAP1 (nBAP1) expression, and their tumour microenvironments (TME) using an “immunoscore” (absent/altered/high) for tumour-infiltrating lymphocytes (TILs) and macrophages (TAMs). Transcriptomes were compared between mUM and control liver; intersegmental and intratumoural analyses were also undertaken. Most mUM were epithelioid cell-type (75%), amelanotic (55%), and nBAP1-ve (70%). They had intermediate (68%) or absent (15%) immunoscores for TILs and intermediate (53%) or high (45%) immunoscores for TAMs. M2-TAMs were dominant in the mUM-TME, with upregulated expression of ANXA1, CD74, CXCR4, MIF, STAT3, PLA2G6, and TGFB1. Compared to control liver, mUM showed significant (p < 0.01) upregulation of 10 genes: DUSP4, PRAME, CD44, IRF4/MUM1, BCL2, CD146/MCAM/MUC18, IGF1R, PNMA1, MFGE8/lactadherin, and LGALS3/Galectin-3. Protein expression of DUSP4, CD44, IRF4, BCL-2, CD146, and IGF1R was validated in all mUMs, whereas protein expression of PRAME was validated in 10% cases; LGALS3 stained TAMs, and MFGEF8 highlighted bile ducts only. Intersegmental mUMs show differing transcriptomes, whereas those within a single mUM were similar. Our results show that M2-TAMs dominate mUM-TME with upregulation of genes contributing to immunosuppression. mUM significantly overexpress genes with targetable signalling pathways, and yet these may differ between intersegmental lesions.

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“…In cutaneous melanoma, DC pulsed with shared antigen peptides did not show evidence for benefit [ 25 ]. However, important adjuvant dendritic cell vaccination randomized trials for skin melanoma (NCT02993315) and uveal melanoma [ 26 ] are ongoing.…”

Section: Discussionmentioning

confidence: 99%

A randomized phase II clinical trial of dendritic cell vaccination following complete resection of colon cancer liver metastasis

Rodríguez¹,

Castañón²,

Perez-Gracia³

et al. 2018

j. immunotherapy cancer

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Surgically resectable synchronic and metachronic liver metastases of colon cancer have high risk of relapse in spite of standard-of-care neoadjuvant and adjuvant chemotherapy regimens. Dendritic cell vaccines loaded with autologous tumor lysates were tested for their potential to avoid or delay disease relapses (NCT01348256). Patients with surgically amenable liver metastasis of colon adenocarcinoma (n = 19) were included and underwent neoadjuvant chemotherapy, surgery and adjuvant chemotherapy. Fifteen patients with disease-free resection margins were randomized 1:1 to receive two courses of four daily doses of dendritic cell intradermal vaccinations versus observation. The trial had been originally designed to include 56 patients but was curtailed due to budgetary restrictions. Follow-up of the patients indicates a clear tendency to fewer and later relapses in the vaccine arm (median disease free survival –DFS-) 25.26 months, 95% CI 8.74-n.r) versus observation arm (median DFS 9.53 months, 95% CI 5.32–18.88).Electronic supplementary materialThe online version of this article (10.1186/s40425-018-0405-z) contains supplementary material, which is available to authorized users.

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Adjuvant Dendritic Cell Vaccination in High-Risk Uveal Melanoma

Cited by 43 publications

References 5 publications

The Role of Immune Checkpoint Blockade in Uveal Melanoma

The Role of Immune Checkpoint Blockade in Uveal Melanoma

Transcriptome Profiling Reveals New Insights into the Immune Microenvironment and Upregulation of Novel Biomarkers in Metastatic Uveal Melanoma

A randomized phase II clinical trial of dendritic cell vaccination following complete resection of colon cancer liver metastasis

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