Calreticulin exposure on malignant blasts predicts a cellular anticancer immune response in patients with acute myeloid leukemia

Wémeau, Mathieu; Kepp, Oliver; Tesnière, Antoine; Panaretakis, Theocharis; Flament, Caroline; Botton, Stéphane de; Zitvogel, Laurence; Chaput, Nathalie

doi:10.1038/cddis.2010.82

Cited by 114 publications

(95 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, we found tumoral CALR levels to positively correlate with the levels of genes relevant for phagosome maturation or processing in only the clinical ICD set-up. Interestingly, elevated levels of phosphorylated eIF2a have been shown to correlate with higher ecto-CRT on malignant myleoblasts from patients with acute myeloid leukaemia regardless of chemotherapy; and higher ecto-CRT correlated with ability of autologous T cells to secrete IFN-g on stimulation with blast-derived dendritic cell and better overall survival of the patients (Wemeau et al, 2010). This observation suggests that ER stress-regulated ecto-CRT is associated with the stimulation of anticancer immunity and may harbour a prognostic role in cancer patients.…”

Section: Surface Exposure Of Particular Chaperonesmentioning

confidence: 99%

Immunogenic cell death

Dudek-Perić²,

et al. 2015

View full text Add to dashboard Cite

Currently, it is widely acknowledged that a proactive anticancer immunosurveillance mechanism takes part in the rejection of neoplastic lesions before they progress towards a benign or malignant tumour. However in cases of very aggressive neoplastic lesions consisting of cells with high mutational diversity, cancer cell variants might be formed that are capable of evading host defence systems against uncontrolled proliferation and anticancer immunosurveillance. This is mainly accomplished through the exhibition of low immunogenicity, which is a particularly important stumbling block in the revival of long-lasting as well as stable anticancer immunity. Recently, it has emerged emphatically that inciting a cancer cell death routine, associated with the activation of danger signalling pathways evoking emission of damage-associated molecular patterns (DAMPs), markedly increases the immunogenicity of dying cancer cells. This cell death pathway has been termed "immunogenic cell death" (ICD). In the present review we introduce this concept and discuss its characteristics in detail. We also discuss in detail the various molecular, immunological and operational determinants of ICD. KEY WORDS: immunogenicity, immunogenic cell death, cancer, danger signals, antigen, damage-associated molecular patterns, danger signalling, ER stress, photodynamic therapy (PDT), chemotherapy Immunogenic cell death: the conceptMost newly formed neoplastic lesions in our body are readily rejected by the host defence system. It is now widely acknowledged that a proactive anticancer immunosurveillance mechanism takes part in rejection of neoplastic lesions before they progress towards a benign or malignant tumour (Dunn et al., 2002, Senovilla et al., 2012. However in cases of very aggressive neoplastic lesions consisting of cells with high mutational diversity; cancer cell variants might be formed that are capable of evading host defence systems against uncontrolled proliferation and anticancer immunosurveillance (Dunn et al., 2002, Zitvogel et al., 2006. In such a scenario, the host immune system might start acting as a "natural selection force" by performing cancer immunoediting, which might lead to the formation of cancer cells that are highly immunoevasive and capable of resisting antitumour immunity (Dunn et al., 2002). Overall resistance against the host anticancer immunosurveillance and antitumour immunity is achieved by various mechanisms including, acquaintance of low immunogenicity, ability to induce immunotolerance or active immunosuppression, and ability to resist immune cell-mediated lysis (Dunn et al., 2002, Garg et al., 2013b, Zitvogel et al., 2006. Here, the exhibition of low immunogenicity is a particularly important stumbling block in the revival Int. J. Dev. Biol. 59: 131-140 (2015) doi: 10.1387/ijdb.150061pa Abbreviations used in this paper: ATP, adenosine triphosphate; CD, cluster of differentiation; CAAs, cancer associated antigens; CRT, calreticulin; DAMP, damageassociated molecular pattern; DC, dendritic cell; ...

show abstract

Section: Surface Exposure Of Particular Chaperonesmentioning

confidence: 99%

Immunogenic cell death

Dudek-Perić²,

et al. 2015

View full text Add to dashboard Cite

show abstract

“…17,[27][28][29] Antigen retrieval was performed by incubating slides in citrate buffer (pH 7.3) for 20 min at 98 C and cooling them for 30 min, at room temperature (RT). The sections were mounted on Shandon Sequenza coverplates (Thermo Fisher Scientific, 72-199-50) in distilled water.…”

Section: Phospho-eif2amentioning

confidence: 99%

The ratio of CD8⁺/FOXP3 T lymphocytes infiltrating breast tissues predicts the relapse of ductal carcinoma in situ

Semeraro¹,

Adam

Stoll³

et al. 2016

OncoImmunology

View full text Add to dashboard Cite

In a series of 248 tumor samples obtained from image-guided biopsies from patients diagnosed with ductal carcinoma in situ of the breast, we attempted to identify biomarkers that predict microinfiltration at definitive surgery or relapse during follow-up. For this, we used immunohistochemical methods, followed by automated image analyses, to measure the mean diameter of nuclei (which correlates with ploidy), the phosphorylation of eukaryotic initiation factor 2a (eIF2a, which reflects endoplasmic reticulum stress) as well as the density and ratio of CD8 C cytotoxic T lymphocytes and FOXP3 C regulatory T cells. The median nuclear diameter of malignant cells correlated with eIF2a phosphorylation (in cancerous tissue), which in turn correlated with the density of the CD8 C infiltrate and the CD8 C /FOXP3 ratio (both in cancerous and the adjacent non-cancerous parenchyma). Neither microinfiltration nor lymph node involvement was associated with the probability of relapse. Both correlated positively with the CD8 C /FOXP3 ratio in the malignant area. In contrast, relapse was associated with a paucity of the CD8 C infiltrate as well as an unfavorable CD8 C /FOXP3 ratio, both in malignant and non-malignant parenchyma. The combined analysis of the CD8 C /FOXP3 ratio in cancerous and non-cancerous tissues revealed a significant impact of their interaction on the probability of relapse, but not on the presence of microinfiltration or lymph node metastasis. Altogether, these results support the idea of an immunosurveillance system that determines the risk of relapse in ductal carcinoma in situ of the breast.

show abstract

“…A limited number of retrospective studies carried out in human cancer patients to ascertain whether ICD-associated parameters can be used as prognostic biomarkers, have yielded contradictory results. [28][29][30][31][32][33][34][35] Possible reasons for this could be restriction to a few ICDderived biomarkers (mainly calreticulin, HMGB1 or CD73), the limited number of patients and variations related to cancer-types.…”

Section: Introductionmentioning

confidence: 99%

Immunological metagene signatures derived from immunogenic cancer cell death associate with improved survival of patients with lung, breast or ovarian malignancies: A large-scale meta-analysis

2015

View full text Add to dashboard Cite

The emerging role of the cancer cell-immune cell interface in shaping tumorigenesis/anticancer immunotherapy has increased the need to identify prognostic biomarkers. Henceforth, our primary aim was to identify the immunogenic cell death (ICD)-derived metagene signatures in breast, lung and ovarian cancer that associate with improved patient survival. To this end, we analyzed the prognostic impact of differential gene-expression of 33 pre-clinically-validated ICD-parameters through a large-scale metaanalysis involving 3,983 patients ('discovery' dataset) across lung (1,432), breast (1,115) and ovarian (1,436) malignancies. The main results were also substantiated in 'validation' datasets consisting of 818 patients of same cancer-types (i.e. 285 breast/274 lung/259 ovarian). The ICD-associated parameters exhibited a highly-clustered and largely cancer type-specific prognostic impact. Interestingly, we delineated ICDderived consensus-metagene signatures that exhibited a positive prognostic impact that was either cancer type-independent or specific. Importantly, most of these ICD-derived consensus-metagenes (acted as attractor-metagenes and thereby) 'attracted' highly co-expressing sets of genes or convergentmetagenes. These convergent-metagenes also exhibited positive prognostic impact in respective cancer types. Remarkably, we found that the cancer type-independent consensus-metagene acted as an 'attractor' for cancer-specific convergent-metagenes. This reaffirms that the immunological prognostic landscape of cancer tends to segregate between cancer-independent and cancer-type specific gene signatures. Moreover, this prognostic landscape was largely dominated by the classical T cell activity/ infiltration/function-related biomarkers. Interestingly, each cancer type tended to associate with biomarkers representing a specific T cell activity or function rather than pan-T cell biomarkers. Thus, our analysis confirms that ICD can serve as a platform for discovery of novel prognostic metagenes.

show abstract

Calreticulin exposure on malignant blasts predicts a cellular anticancer immune response in patients with acute myeloid leukemia

Cited by 114 publications

References 41 publications

Immunogenic cell death

Immunogenic cell death

The ratio of CD8⁺/FOXP3 T lymphocytes infiltrating breast tissues predicts the relapse of ductal carcinoma in situ

Immunological metagene signatures derived from immunogenic cancer cell death associate with improved survival of patients with lung, breast or ovarian malignancies: A large-scale meta-analysis

Contact Info

Product

Resources

About

Calreticulin exposure on malignant blasts predicts a cellular anticancer immune response in patients with acute myeloid leukemia

Cited by 114 publications

References 41 publications

Immunogenic cell death

Immunogenic cell death

The ratio of CD8+/FOXP3 T lymphocytes infiltrating breast tissues predicts the relapse of ductal carcinoma in situ

Immunological metagene signatures derived from immunogenic cancer cell death associate with improved survival of patients with lung, breast or ovarian malignancies: A large-scale meta-analysis

Contact Info

Product

Resources

About

The ratio of CD8⁺/FOXP3 T lymphocytes infiltrating breast tissues predicts the relapse of ductal carcinoma in situ