Clinicopathological and Prognostic Significance of PRAME Overexpression in Human Cancer: A Meta-Analysis

Li, Jiaqiang; Yin, Jianchun; Zhong, Jian; Yang, Zhilin; Tang, Aifa; Li, Shoulin

doi:10.1155/2020/8828579

Cited by 29 publications

(33 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1,2 Aberrantly high levels of PRAME expression are seen in some malignancies, including melanoma, some sarcomas and hematologic neoplasms, and several solid organ tumors. 1,3 Although the pathophysiological function of PRAME is currently unclear, it is known that it inhibits retinoic acid receptor signaling and the transcription of some genes involved in growth arrest, differentiation, and apoptosis. 2,3 PRAME hypomethylation is seen in malignant cells, 2 while knockdown/ downregulation has been shown to decrease cancer cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

“…1,3 Although the pathophysiological function of PRAME is currently unclear, it is known that it inhibits retinoic acid receptor signaling and the transcription of some genes involved in growth arrest, differentiation, and apoptosis. 2,3 PRAME hypomethylation is seen in malignant cells, 2 while knockdown/ downregulation has been shown to decrease cancer cell proliferation. 3 This property, along with its restricted expression profile in normal tissue types and high immunogenicity, has made PRAME a potential biomarker candidate for cancer immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 PRAME hypomethylation is seen in malignant cells, 2 while knockdown/ downregulation has been shown to decrease cancer cell proliferation. 3 This property, along with its restricted expression profile in normal tissue types and high immunogenicity, has made PRAME a potential biomarker candidate for cancer immunotherapy. 3 In this report, we describe a case of an ambiguous melanocytic proliferation arising in a giant congenital melanocytic nevus (CMN) and outline the potential utility of an immunohistochemical study with PRAME in differentiating benign proliferative nodules (PN) from melanoma in this context.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Diagnostic utility of PRAME in distinguishing proliferative nodules from melanoma in giant congenital melanocytic nevi

et al. 2021

View full text Add to dashboard Cite

We describe a case of a melanocytic proliferation arising in a giant congenital melanocytic nevus (CMN) and outline the potential utility of an immunohistochemical study with PReferentially expressed Antigen in MElanoma (PRAME) in distinguishing benign proliferative nodules (PN) from melanoma in this context. A 15-day-old girl presented with a fibrotic nodule clinically suspicious for melanoma within a giant CMN. Histopathological examination showed a predominantly intradermal melanocytic nevus with congenital features intermixing with an ill-defined proliferation of larger melanocytes demonstrating mild-to-moderate cytologic atypia and increased mitotic activity. Anti-PRAME was diffusely positive within the congenital nevus while negative within the larger proliferating cells. Chromosomal microarray analysis revealed whole chromosomal gains and losses only, consistent with a PN arising in a giant CMN. To our knowledge, PRAME expression in giant CMN, PN, and pediatric melanomas has not been previously described. Based on our experience with this case, we propose that differential patterns of PRAME expression may be present in these three lesions, allowing PRAME immunohistochemistry to potentially serve as a helpful adjunct diagnostic tool for laboratories that do not readily have access to molecular testing in rendering a diagnosis for atypical melanocytic proliferations arising in giant CMN.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Diagnostic utility of PRAME in distinguishing proliferative nodules from melanoma in giant congenital melanocytic nevi

et al. 2021

View full text Add to dashboard Cite

show abstract

“…PRAME expression has been demonstrated in a variety of solid and haematological malignancies 3‐6 . High PRAME tumour expression has been associated with poor prognosis in several solid tumours, increased risk of metastases and shorter disease‐free and overall survival, 7 whereas it has been found to predict a more favourable outcome in acute myeloid and lymphoblastic leukaemia 5,8‐12 . Several studies suggest that PRAME can induce cell proliferation, reduce cytotoxic drug sensitivity and inhibit apoptosis in a variety of cancers 13‐16 .…”

Section: Introductionmentioning

confidence: 99%

Cancer testis antigen PRAME: An anti‐cancer target with immunomodulatory potential

Belič

Thomas

Al-Khadairi

et al. 2021

J Cellular Molecular Medi

View full text Add to dashboard Cite

PReferentially expressed Antigen in Melanoma (PRAME) is a cancer testis antigen with restricted expression in somatic tissues and re‐expression in poor prognostic solid tumours. PRAME has been extensively investigated as a target for immunotherapy, however, its role in modulating the anti‐tumour immune response remains largely unknown. Here, we show that PRAME tumour expression is associated with worse survival in the TCGA breast cancer cohort, particularly in immune‐unfavourable tumours. Using direct and indirect co‐culture models, we found that PRAME overexpressing MDA‐MB‐468 breast cancer cells inhibit T cell activation and cytolytic potential, which could be partly restored by silencing of PRAME. Furthermore, silencing of PRAME reduced expression of several immune checkpoints and their ligands, including PD‐1, LAG3, PD‐L1, CD86, Gal‐9 and VISTA. Interestingly, silencing of PRAME induced cancer cell killing to levels similar to anti‐PD‐L1 atezolizumab treatment. Comprehensive analysis of soluble inflammatory mediators and cancer cell expression of immune‐related genes showed that PRAME tumour expression can suppress the expression and secretion of multiple pro‐inflammatory cytokines, and mediators of T cell activation, differentiation and cytolysis. Together, our data indicate that targeting of PRAME offers a potential, novel dual therapeutic approach to specifically target tumour cells and regulate immune activation in the tumour microenvironment.

show abstract

“…Tebentafusp is expected to achieve regulatory approval soon and is already accessible within an international compassionate use program. Two other ImmTACs are in phase 2 testing, namely IMC-C103C for MAGE-A4-derived peptides [ 169 ] (NCT03973333), and IMC-F106C for “preferentially expressed antigen in melanoma” (PRAME [ 170 ])-positive tumors (NCT04262466), both exploiting the HLA-A2 background present in approximately 50% of Caucasian patients [ 171 ].…”

Section: Bispecific Antibodiesmentioning

confidence: 99%

Principles and Current Clinical Landscape of Multispecific Antibodies against Cancer

Elshiaty

Schindler

Christopoulos

2021

IJMS

View full text Add to dashboard Cite

Building upon the resounding therapeutic success of monoclonal antibodies, and supported by accelerating progress in engineering methods, the field of multispecific therapeutic antibodies is growing rapidly. Over 140 different molecules are currently in clinical testing, with excellent results in recent phase 1–3 clinical trials for several of them. Multivalent bispecific IgG-modified formats predominate today, with a clear tendency for more target antigens and further increased valency in newer constructs. The strategies to augment anticancer efficacy are currently equally divided between disruption of multiple surface antigens, and additional redirection of cytotoxic T or NK lymphocytes against the tumor. Both effects complement other modern modalities, such as tyrosine kinase inhibitors and adoptive cell therapies, with which multispecifics are increasingly applied in combination or merged, for example, in the form of antibody producing CAR-T cells and oncolytics. While mainly focused on B-cell malignancies early on, the contemporary multispecific antibody sector accommodates twice as many trials against solid compared to hematologic cancers. An exciting emerging prospect is the targeting of intracellular neoantigens using T-cell receptor (TCR) fusion proteins or TCR-mimic antibody fragments. Considering the fact that introduction of PD-(L)1 inhibitors only a few years ago has already facilitated 5-year survival rates of 30–50% for per se highly lethal neoplasms, such as metastatic melanoma and non-small-cell lung carcinoma, the upcoming enforcement of current treatments with “next-generation” immunotherapeutics, offers a justified hope for the cure of some advanced cancers in the near future.

show abstract

Clinicopathological and Prognostic Significance of PRAME Overexpression in Human Cancer: A Meta-Analysis

Cited by 29 publications

References 28 publications

Diagnostic utility of PRAME in distinguishing proliferative nodules from melanoma in giant congenital melanocytic nevi

Diagnostic utility of PRAME in distinguishing proliferative nodules from melanoma in giant congenital melanocytic nevi

Cancer testis antigen PRAME: An anti‐cancer target with immunomodulatory potential

Principles and Current Clinical Landscape of Multispecific Antibodies against Cancer

Contact Info

Product

Resources

About