Discovery and Validation of Protein Abundance Differences between Follicular Thyroid Neoplasms

Netea‐Maier, Romana T.; Hunsucker, Stephen W.; Hoevenaars, Brigiet M.; Helmke, Steve M.; Slootweg, Pieter J.; Hermus, A.R.M.M.; Haugen, Bryan R.; Duncan, Mark W.

doi:10.1158/0008-5472.can-07-5020

Cited by 50 publications

(35 citation statements)

References 33 publications

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“…Therefore, primary tumor cells may be less prone to undergo immunogenic cell death compared with in vitro established cell lines. Accordingly, the ability to downregulate CRT expression has been shown to be associated with a negative prognostic/predictive effect in colon cancer (28), neuroblastoma (29), and cervical carcinoma (30), as well as in follicular thyroid carcinoma (31). Nevertheless, our in vitro models consistently showed CRT and HSP90 cell surface translocation are the distinctive features induced by the combined exposure to HS, γ, and UVC.…”

Section: Discussionmentioning

confidence: 70%

Improved Clinical Outcome in Indolent B-Cell Lymphoma Patients Vaccinated with Autologous Tumor Cells Experiencing Immunogenic Death

et al. 2010

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Increasing evidence argues that the success of an anticancer treatment may rely on immunoadjuvant side effects including the induction of immunogenic tumor cell death. Based on the assumption that this death mechanism is a similar prerequisite for the efficacy of an active immunotherapy using killed tumor cells, we examined a vaccination strategy using dendritic cells (DC) loaded with apoptotic and necrotic cell bodies derived from autologous tumors. Using this approach, clinical and immunologic responses were achieved in 6 of 18 patients with relapsed indolent non-Hodgkin's lymphoma (NHL). The present report illustrates an impaired ability of the neoplastic cells used to vaccinate nonresponders to undergo immunogenic death on exposure to a cell death protocol based on heat shock, γ-ray, and UVC ray. Interestingly, when compared with doxorubicin, this treatment increased surface translocation of calreticulin and cellular release of high-mobility group box 1 and ATP in histologically distinct NHL cell lines. In contrast, treated lymphoma cells from responders displayed higher amounts of calreticulin and heat shock protein 90 (HSP90) compared with those from nonresponders and boosted the production of specific antibodies when loaded into DCs for vaccination. Accordingly, the extent of calreticulin and HSP90 surface expression in the DC antigenic cargo was significantly associated with the clinical and immunologic responses achieved. Our results indicate that a positive clinical effect is obtained when immunogenically killed autologous neoplastic cells are used for the generation of a DC-based vaccine. Therapeutic improvements may thus be accomplished by circumventing the tumor-impaired ability to undergo immunogenic death and prime the antitumor immune response. Cancer Res; 70(22); 9062-72. ©2010 AACR.

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Section: Discussionmentioning

confidence: 70%

Improved Clinical Outcome in Indolent B-Cell Lymphoma Patients Vaccinated with Autologous Tumor Cells Experiencing Immunogenic Death

et al. 2010

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“…In this context, it seems intriguing that reduced calreticulin expression constitutes a negative prognostic/predictive feature of colon cancers (Toquet et al, 2007). Reduced calreticulin expression also has a negative impact on neuroblastoma (Hsu et al, 2005), cervical carcinoma (Mehta et al, 2008), as well as on follicular thyroid carcinoma (Netea-Maier et al, 2008). Hence, it will be important to investigate whether CRT affects the immunogenicity of such tumors beyond its role in contributing to optimal peptide loading into major histocompatibility complex class I antigen (Wright et al, 2004;Zhang and Williams, 2006).…”

Section: Discussionmentioning

confidence: 99%

Immunogenic death of colon cancer cells treated with oxaliplatin

et al. 2009

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Both the pre-apoptotic exposure of calreticulin (CRT) and the post-apoptotic release of high-mobility group box 1 protein (HMGB1) are required for immunogenic cell death elicited by anthracyclins. Here, we show that both oxaliplatin (OXP) and cisplatin (CDDP) were equally efficient in triggering HMGB1 release. However, OXP, but not CDDP, stimulates pre-apoptotic CRT exposure in a series of murine and human colon cancer cell lines. Subcutaneous injection of OXP-treated colorectal cancer (CRC), CT26, cells induced an anticancer immune response that was reduced by short interfering RNAmediated depletion of CRT or HMGB1. In contrast, CDDP-treated CT26 cells failed to induce anticancer immunity, unless recombinant CRT protein was absorbed into the cells. CT26 tumors implanted in immunocompetent mice responded to OXP treatment in vivo, and this therapeutic response was lost when CRT exposure by CT26 cells was inhibited or when CT26 cells were implanted in immunodeficient mice. The knockout of toll-like receptor 4 (TLR4), the receptor for HMGB1, also resulted in a deficient immune response against OXP-treated CT26 cells. In patients with advanced (stage IV, Duke D) CRC, who received an OXP-based chemotherapeutic regimen, the loss-of-function allele of TLR4 (Asp299Gly in linkage disequilibrium with Thr399Ile, reducing its affinity for HMGB1) was as prevalent as in the general population. However, patients carrying the TLR4 loss-of-function allele exhibited reduced progression-free and overall survival, as compared with patients carrying the normal TLR4 allele. In conclusion, OXP induces immunogenic death of CRC cells, and this effect determines its therapeutic efficacy in CRC patients.

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“…CALR expression was found to be lower in malignant follicular thyroid carcinoma compared with benign follicular thyroid adenoma using proteomics analysis validated by immunohistochemistry (Netea-Maier, et al 2008). …”

Section: Thyroid Cancermentioning

confidence: 99%

CALR (calreticulin)

Machado-Neto¹,

Campos²,

Trainaen³

2018

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Calreticulin (CALR) is a multifunctional protein involved in molecular chaperoning and calcium homeostasis. CALR has also been associated with proliferation, cell cycle progression, migration, invasion and anoikis resistance in cancer cells. The prognostic impact of CALR expression is yet to be elucidated, however in some types of cancer, high CALR expression has been related to worse clinical outcomes. Notably, the discovery of recurrent mutations in the exon 9 of the CALR gene in myeloproliferative neoplasms has opened a new round of investigations. The present review contains data on CALR DNA/RNA, protein encoded and function.

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Discovery and Validation of Protein Abundance Differences between Follicular Thyroid Neoplasms

Cited by 50 publications

References 33 publications

Improved Clinical Outcome in Indolent B-Cell Lymphoma Patients Vaccinated with Autologous Tumor Cells Experiencing Immunogenic Death

Improved Clinical Outcome in Indolent B-Cell Lymphoma Patients Vaccinated with Autologous Tumor Cells Experiencing Immunogenic Death

Immunogenic death of colon cancer cells treated with oxaliplatin

CALR (calreticulin)

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