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Introduction: Novel breast cancer risk-reducing strategies for individuals with germline mutations of the BRCA1 and/or BRCA2 genes are urgently needed. Identification of antigenic targets that are expressed in early cancers, but absent in normal breast epithelium of these high-risk individuals, could provide the basis for the development of effective immunoprophylactic strategies. Cancer testis (CT) antigens are potential candidates because their expression is restricted to tumors, and accumulating data suggest that they play important roles in cellular proliferation, stem cell function, and carcinogenesis. The objective of this study was to examine the expression of CT antigens and their frequency in BRCA-associated breast cancers. Methods: Archived breast cancer tissues ( n = 26) as well as morphologically normal breast tissues ( n = 7) from women carrying deleterious BRCA 1 and/or 2 mutations were obtained for antigen expression analysis by immunohistochemistry. Expression of the following CT antigens was examined: MAGE-A1, MAGE-A3, MAGE-A4, MAGE-C1.CT7, NY-ESO-1, MAGE-C2/CT10, and GAGE. Results: CT antigens were expressed in 16/26 (61.5%, 95% CI 43-80%) of BRCA-associated cancers, including in situ tumors. Thirteen of twenty-six (50%) breast cancers expressed two or more CT antigens; three cancers expressed all seven CT antigens. MAGE-A was expressed in 13/26 (50%) of cancers, NY-ESO-1 was expressed in 10/26 (38%) of tumors. In contrast, none of the CT antigens were expressed in adjacent or contralateral normal breast epithelium ( P = 0.003). Conclusions: We report a high CT antigen expression rate in BRCA-associated breast cancer as well as the lack of expression of these antigens in benign breast tissue of carriers, identifying CT antigens as potential vaccine targets for breast cancer prevention in these high-risk individuals. [ABSTRACT FROM AUTHOR]

The melanoma antigen (MAGE) family proteins are well known as tumor-specific antigens and comprise more than 60 genes, which share a conserved MAGE homology domain (MHD). Type I MAGEs are highly expressed cancer antigens, and they play an important role in tumorigenesis and cancer cell survival. Recently, several MAGE proteins were identified to interact with RING domain proteins, including a sub-family of E3 ubiquitin ligases. The binding mode between MAGEs and RING proteins was investigated and one important structure of these MAGE-RING complexes was solved: the MAGE-G1-NSE1 complex. Structural and biochemical studies indicated that MAGE proteins could adjust the E3 ubiquitin ligase activity of its cognate RING partner both in vitro and in vivo. However, the underlying mechanism was not fully understood. Here, we review these exciting advances in the studies on MAGE family, suggest potential mechanisms by which MAGEs activate the E3 activity of their binding RING proteins and highlight the anticancer potential of this family proteins. [ABSTRACT FROM AUTHOR]

We previously described PASD1 as a new cancer testis antigen in multiple myeloma (MM) that is retained post-therapy, suggesting the use of vaccination strategies to induce anti-PASD1 immunity in a setting of minimal residual disease. We have focused on DNA fusion gene vaccines, coupling fragment C domain (DOM) of tetanus toxin with PASD1 sequence, and examined efficacy in Human Leukocyte Antigen (HLA)-A2 (HHD) transgenic mice using a human MM cell line expressing PASD1 protein and chimeric HLA-A2 class I molecules as target. DNA vaccines encoded two HLA-A2-restricted epitopes (p.DOM-PASD1(1), p.DOM-PASD1(2)) and full-length PASD1 (p.DOM-PASD1FL). p.DOM-PASD1(1) proved superior to p.DOM-PASD1(2) in generating T-cell responses in HHD mice, able to lyse the chimeric murine RMA-HHD cells. Boosting by electroporation significantly enhanced p.DOM-PASD1(1). Only p.DOM-PASD1(1) induced cytotoxic T-lymphocytes (CTLs) were able to lyse human MM target cells expressing endogenous antigen. The p.DOM-PASD1FL vaccine predominantly induced strong PASD1(1) over PASD1(2) T-cell immune responses, indicative of immunodominance. Importantly, p.DOM-PASD1FL generated immune-mediating killing of native chimeric MM cells, in the absence of exogenous added peptide, implicating PASD1(1) specific CTLs. These data demonstrate that PASD1-derived epitopes are both efficiently and selectively processed and presented by native human MM cells. Notably, they permit the use of PASD1-encoding DNA vaccine therapy in a clinical setting. [ABSTRACT FROM AUTHOR]

Abstract: Early diagnosis and cure for patients with chronic myeloid leukemia (CML) exhibit significant clinical challenges because of the disease progression from chronic phase (CP) into a rapidly fatal blast crisis. Our earlier studies suggested an association of sperm associated antigen 9 (SPAG9) with various human malignancies. The present investigation revealed that SPAG9 mRNA and protein are expressed in CML patients (88%), in K562 and KCL-22 cells. Further, SPAG9 protein expression was also detected on cell surface suggesting that this molecule may be a suitable target for immunotherapy. Interestingly, 90% CML-CP patients showed humoral response against SPAG9, suggesting its important role in early diagnostic of CML-CP. Further investigation is warranted in establishing the potential of SPAG9 as a biomarker and immunotherapeutic target for early treatment of CML-CP patients. [Copyright &y& Elsevier]

Background and Aims: Screening methods for early detection of prostate cancer have some limitations regarding specificity and sensitivity, so there is a continuing search to find new cancer biomarkers. Cancer-testis genes are a group of genes with expression almost limited to testis and different kinds of tumors. Since testis is an immune privileged site, if these genes are expressed in tumors, they can be immunogenic. We undertook this study to find new members of the cancer-testis gene family appropriate for cancer immunotherapy Methods: We analyzed the expression of six testis-specific genes called ODF1, ODF2, ODF3, ODF4, LEMD1 and SPATA19 in 30 prostate cancer and 25 benign prostate hyperplasia (BPH) samples by RT-PCR and restriction fragment length polymorphism (RFLP). Results: Of the prostate cancer samples, 10, 10, 23 and 40% showed ODF1, ODF2, LEMD1 and SPATA19 specific bands, respectively, but none of the BPH samples expressed any of these genes. The difference between prostate cancer and BPH groups for LEMD1 and SPATA19 expression was significant. Mean serum PSA level was significantly higher in patients expressing ODF2 than in the other patients. Conclusions: ODF1, ODF2, SPATA19 and LEMD1 are members of cancer-testis gene family. In addition, LEMD1 and SPATA19 are putative cancer biomarkers and promising targets for active immunotherapy. [Copyright &y& Elsevier]

The identification of immunogenic cancer testis antigens (CTAs) as immunotherapeutic targets represents one approach to improve treatment options for diffuse large B-cell lymphoma (DLBCL). We previously identified PASD1 [PAS (Per ARNT Sim) domain containing 1 (PASD1)], a DLBCL-associated CTA that was expressed in a range of hematopoietic malignancies. The aim of the present study was to investigate the presence of a cytotoxic T-cell (CTL) response to PASD1 in DLBCL patients. A significant γ-interferon (IFN) release was detected in 21/29 HLA-A*0201-positive DLBCL patients (18 de novo DLBCL, two transformed DLBCL and one T-cell rich B-cell lymphoma) following short-term culture of their peripheral blood mononuclear cells stimulated with five HLA-A*0201-restricted PASD1 peptides. No significant responses were detected in 21 HLA-A*0201-negative DLBCL patients (12 de novo DLBCL, seven transformed DLBCL, two T-cell rich B-cell lymphoma) or six normal subjects. CTL cell lines were able to lyse PASD1-positive tumour cells in a major histocompatibility complex-Class I dependent manner. The presence of a γ-IFN response correlated with PASD1 protein expression in the tumour cells in 12/15 cases studied. This is the first report of a CTL response to a CTA in DLBCL. Our results provide additional valuable evidence supporting PASD1 as a potential immunotherapeutic target for the treatment of DLBCL and other malignancies. [ABSTRACT FROM AUTHOR]

The article presents the study conducted by the researchers regarding the clinical utility of sperm-associated antigen 9 (SPAG9) expression and its humoral immune response in an early cervical carcinomas. The study aims to determine the association of SPAG9 in ovarian cancer using the reverse transcriptase-polymerase chain reaction and situ RNA hybridization. The result shows that patients with the early stage of cancer can generate SPAG9 antibodies and exhibit SPAG9 expression.

Surgical resection represents the treatment of choice for primary melanoma, providing the best results, in terms of long-term survival, for thin lesions. However, surgery has limited efficacy in the management of locoregional and distant metastases, as do chemotherapy and radiotherapy. In this context, immunotherapy is a promising and additional therapeutic option to cure melanoma patients and to prevent relapse of the disease. The identification and characterization of immunogenic tumor-associated antigens (TAAs) has prompted the design and development of a plethora of therapeutic vaccines to drive the host immune system to specifically recognize and eradicate neoplastic cells. Although encouraging, clinical results obtained with TAA-based vaccination are not yet satisfactory. In this regard, a great number of experimental data indicate that neoplastic cells are capable of escaping the host's immune surveillance and impairing the efficacy of immunotherapeutic approaches by different mechanisms. Among these, the epigenetic editing of gene-expression patterns by aberrant DNA hypermethylation and/or histone deacetylation is emerging as a frequent and important tool employed by melanoma cells to trigger the downregulation of the components of the tumor presentation/recognition complex. This review will summarize the available data derived from preclinical and clinical research using epigenetic drugs, such as histone deacetylase and DNA methyltransferase inhibitors, to revert epigenetic alterations, and the current knowledge of the potential immunotherapeutic implications of epigenetic treatment in the melanoma clinic. [ABSTRACT FROM AUTHOR]

Abstract: The cancer testis (CT) antigen HCA587 is highly expressed in human hepatocellular carcinoma (HCC) and induces specific T-cell responses in a significant proportion of HCC patients. To explore its potential in cancer immunotherapy, a reverse immunology approach was adopted to identify HCA587-derived HLA-A∗0201-restricted epitopes. Multiple peptides with a top ranking in various prediction programs were thus synthesized and three of them—p248–256, p140–149 and p144–152—were found to bind to HLA-A*0201 molecules with a high affinity and effectively induced a recall response of CD8+ T cells, which were either primed in vitro with the HCA587 antigen or directly isolated from HCC patients bearing HCA587+ tumors. Notably, these peptide-specific CD8+ T cells exhibited potent cytotoxic activity over HCA587+ tumor cells. Taken together, the present study has identified three new HLA-A*0201-restricted cytotoxic T cell epitopes in the CT antigen HCA587, which may serve as targets for peptide-based immunotherapy for HCC patients. [Copyright &y& Elsevier]

Abstract: SSX2 is a cancer testis antigen expressed in a wide variety of cancers, including synovial sarcoma and melanoma. It holds promise as a potential antigen for cancer immunotherapy. A process for the production of recombinant SSX2 was developed by overexpressing a His-tagged fusion protein of SSX2 in Escherichia coli C41 (DE3). A T-7 promoter system was employed and a plasmid was introduced into the strain to compensate for rare codons in the SSX2 sequence. The production of SSX2 was scaled up to a 2-L fermentation that was operated under fed-batch conditions to improve productivity. After 32h cultivation, the wet cell mass reached 260mg/ml, with SSX2 produced mainly as inclusion bodies at a concentration of 1.1g/L. Urea-solubilized SSX2 was purified by nickel affinity, ion exchange and hydrophobic interaction chromatography. The recovery of SSX2 was 20%, and over 87% purity was obtained with an endotoxin level of 0.11EU/μg. The purified recombinant SSX2 was characterized by ELISA and was shown to be recognized by human sera that have been reported to carry anti-SSX2 antibodies. [Copyright &y& Elsevier]

Mitotic centromere-associated kinesin (MCAK) is a microtubule (MT) depolymerase necessary for ensuring proper kinetochore MT attachment during spindle formation. To determine MCAK expression status and its clinicopathological significance, real-time reverse transcriptase-polymerase chain reaction was used in 65 cases of gastric cancer. MCAK gene expression in cancer tissue was significantly higher than expression in non-malignant tissue (P<0.05). Elevated MCAK expression was significantly associated with lymphatic invasion (P=0.01) and lymph node metastasis (P=0.04). Furthermore, patients with high MCAK expression had a significantly poorer survival rate than those with low MCAK expression (P=0.008). Immunohistochemical study revealed that expression of MCAK was primarily observed in cancer cells. Additionally, a gastric cancer cell line (AZ521) that stably expressed MCAK was established and used to investigate the biological effects of the MCAK gene. In vitro results showed that cells transfected with MCAK had a high rate of proliferation (P<0.001) and increased migratory ability (P<0.001) compared to mock-transfected cells. This study demonstrated that elevated expression of MCAK may be associated with lymphatic invasion, lymph node metastasis, and poor prognosis. These characteristics may be due in part to the increased proliferative and migratory ability of cells expressing MCAK. [ABSTRACT FROM AUTHOR]

Abstract: Background: To be effective and selective, immunotherapy ideally targets specifically tumor cells and spares normal tissues. Identification of tumor specific antigens is a prerequisite to establish an effective immunotherapy. Still very little is known about the expression of tumor-related antigens in pancreatic neoplasms. Cancer Testis antigens (CT) are antigens shared by a variety of malignant tumors, but not by normal tissues with the exception of germ cells in testis. Restricted expression in neoplastic tissues and inherent immunogenic features make CT antigens ideal for use in immunotherapy. We analyzed the expression of a selected panel of nine CT antigens that have been proven to elicit an efficient immunogenic response in other malignancies. In addition we analyzed the expression of HERV-K-MEL, an immunogenic antigen of viral origin. Methods: Pancreatic adenocarcinoma tumor samples (n =130) were obtained intraoperatively, control tissues (n =23) were collected from cadaveric donor and from patients with chronic pancreatitis. Tumor-associated antigen expression of MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, LAGE-1, NY-ESO-1, SCP-1, SSX-2, SSX-4 and HERV-K-MEL was assessed by PCR. Sequencing of PCR products were performed to assess the expression of SSX-4 in neoplastic and normal pancreatic tissues. Results: Three of 10 tested antigens were expressed in over 10% of malignant pancreatic tissue samples. SSX-4 was found positive in 30% of cases, SCP-1 in 19% and HERV-K-MEL in 23% of cases. No expression of CT antigens was found in non-malignant pancreatic tissue with the exception of SSX-4 and and SSX-2. Conclusions: Fifty two percentage of the analyzed tissues expressed at least one CT antigen. The concomitant expression of SSX-4 in both malignant and non-malignant pancreatic tissue is a new finding which may raise concerns for immunotherapy. However, HERV-K-MEL is expressed with a relatively high prevalence and may be a candidate for specific immunotherapy in a large subgroup of pancreatic cancer patients. This study advocates the analysis of patients with regard to their immunogenic profile before the onset of antigen-specific immunotherapy. [Copyright &y& Elsevier]

Tumor-infiltrating cytotoxic T lymphocytes (TILs), including CD8 TILs, have been associated with favorable clinical outcomes in multiple tumor types. Tumor-infiltrating CD8 T cells and major histocompatibility complex (MHC) class I expression in urothelial carcinoma (UC) have not been previously reported. Most immune responses are mediated by local cytotoxic lymphocytes (CD8 T cells), which can eradicate tumor cells by recognizing tumor-associated antigens presented by MHC class I molecules. Here we analyzed the presence of intratumoral CD8 T cells, the expression of MHC class I antigen, and the expression of the NY-ESO-1 tumor antigen in UC samples and correlated our findings with clinical outcome. Immunohistochemical staining for intratumoral CD8 T cells in tissue samples from 69 patients with UC showed that patients with advanced UC (pT2, pT3, or pT4) and higher numbers of CD8 TILs within the tumor (≥8) had better disease-free survival (P < 0.001) and overall survival (P = 0.018) than did patients with similar-staged UC and fewer intratumoral CD8 TILs. We conclude that the extent of intratumoral CD8 TILs is an important prognostic indicator in advanced UC. [ABSTRACT FROM AUTHOR]

In a recent report, [Zhang et al. (2003) N. Engl. i. Med. 348,203-213], the presence of CD3+ tumor-infiltrating lymphocytes (TILs) was found to correlate with improved survival in epithelial ovarian cancer. We performed immunohistochemical analysis for TILs and cancer testis antigens in 117 cases of epithelial ovarian cancer. The interrelationship between subpopulations of TILs and expression of cancer testis antigens was investigated, as well as between TILs and overall survival. The median follow-up of the patients was 31 months. Patients with higher frequencies of intraepithelial CD8+ T cells demonstrated improved survival compared with patients with lower frequencies [median = 55 versus 26 months; hazard ratio = 0.33; confidence interval (C.I.) = 0.18-0.60; p = 0.0003]. No association was found for CD3+ TILs or other subtypes of intraepithelial or stromal TILs. However, the subgroups with high versus low intraepithelial CD8+/CD4+ TIL ratios had median survival of 74 and 25 months, respectively (hazard ratio = 0.30; C.I. = 0.16-0.55; P = 0.0001). These results indicate that CD4+ TILs influence the beneficial effects of CD8+ TIL. This unfavorable effect of CD4+ T cells on prognosis was found to be due to CD25+ forkhead box P3 (FOXP3)+ regulatory T cells (Treg; suppressor T cells), as indicated by survival of patients with high versus low CD8+/Treg ratios (median = 58 versus 23 months; hazard ratio = 0.31; C.I. = 0.17-0.58; P = 0.0002). The favorable prognostic effect of intraepithelial CD8+ TILs did not correlate with concurrent expression of NY-ESO-1 or MAGE antigens. We conclude that intraepithelial CD8+ TILs and a high CD8+/Treg ratio are associated with favorable prognosis in epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Here we report that the OX-TES-1 SEREX antigen, which showed immunological reactivity with serum from four out of 10 diffuse large B-cell lymphoma (DLBCL) patients, is encoded by a novel gene, PAS domain containing 1 (PASD1). PASD1_v1 cDNA encodes a 639 amino-acid (aa) protein product, while an alternatively spliced variant (PASD1_v2), lacking intron 14, encodes a 773 aa protein, the first 638 aa of which are common to both proteins. The PASD1-predicted protein contains a PAS domain that, together with a putative leucine zipper and nuclear localisation signal, suggests it encodes a transcription factor. The expression of PASD1_v1 mRNA was confirmed by RT-PCR in seven DLBCL-derived cell lines, while PASD1_v2 mRNA appears to be preferentially expressed in cell lines derived from non-germinal centre DLBCL. Immunophenotyping studies of de novo DLBCL patients' tumours with antibodies to CD10, BCL-6 and MUM1 indicated that two patients mounting an immune response to PASD1 were of a poor prognosis non-germinal centre subtype. Expression of PASD1 mRNA was restricted to normal testis, while frequent expression was observed in solid tumours (25 out of 68), thus fulfilling the criteria for a novel cancer testis antigen. PASD1 has potential for lymphoma vaccine development that may also be widely applicable to other tumour types.British Journal of Cancer (2004) 91, 141-149. doi:10.1038/sj.bjc.6601875 www.bjcancer.com Published online 25 May 2004 [ABSTRACT FROM AUTHOR]

Meiosis facilitates diversity across individuals and serves as a major driver of evolution. However, understanding how meiosis begins is complicated by fundamental differences that exist between sexes and species. Fundamental meiotic research is further hampered by a current lack of human meiotic cells lines. Consequently, much of what we know relies on data from model organisms. However, contextualising findings from yeast, worms, flies and mice can be challenging, due to marked differences in both nomenclature and the relative timing of meiosis. In this review, we set out to combine current knowledge of signalling and transcriptional pathways that control meiosis initiation across the sexes in a variety of organisms. Furthermore, we highlight the emerging links between meiosis initiation and oncogenesis, which might explain the frequent re-expression of normally silent meiotic genes in a variety of human cancers., (© 2021 The Author(s).)

Background & Objective: Glioblastoma is the most common primary malignancy of the brain, the prognosis of which is poor. Immunotherapy with cancer/testis (CT) antigens is a novel therapeutic approach for glioblastoma. This study aimed to investigate the expression rate of MAGE-E1, GAGE, and SOX-6 in glioblastoma tumors using the method of immunohistochemistry (IHC)., Methods: Expression of MAGE-E1, GAGE, and SOX-6 were determined by IHC in 50 paraffin blocks of glioblastoma. The results were compared between variables including age, gender, tumor location, and Karnofsky performance status (Kps) score. Survival analysis was also performed., Results: The expression levels of SOX-6, MAGE-E1, and GAGE were 82%, 78%, and 76%, respectively. The relationship between CT antigens and age, gender, and tumor location was not significant, while the association between MAGE-E1 expression and age was statistically significant ( P =0.002). High expression levels of SOX-6 and MAGE-E1 were associated with low Kps scores ( P =0.034 and P <0.001, respectively). Survival analysis showed that age >40 and Kps score <80 were associated with significant relationship with shorter survival rate. ( P =0.005 and P =0.018, respectively). Expression of MAGE-E1 and GAGE was negatively associated with overall 2-year survival rate ( P =0.001 and P =0.021, respectively)., Conclusion: The expression of all the three CT antigens, especially MAGE-E1 and SOX-6, was high in patients with glioblastoma. It can be concluded that these markers could be ideal targets for immunotherapy in such patients. MAGE-E1 and SOX-6 can be considered as important markers in determining the prognosis of glioblastoma.

Aim: In the present study, we investigated the relationship between the expressions of two cancer testis antigens (CTA), LY6K (lymphocyte antigen 6 complex locus K) and CDCA1 (cell division cycle associated 1), in esophageal squamous cell carcinoma (ESCC) tumors and the long-term outcomes of patients with ESCC to clarify the clinical significance of LY6K and CDCA1 expression in ESCC tumors., Methods: A total of 175 patients with thoracic ESCC who had undergone a thoracic esophagectomy with three-field lymphadenectomy without neoadjuvant therapy were retrospectively reviewed in this study. LY6K and CDCA1 expressions were evaluated in tumor tissues using immunohistochemical (IH) staining., Results: Median patient age was 63 years; 159 patients (90.9%) were men. Ninety-four patients (55.3%) were LY6K-positive, and 85 patients (48.6%) were CDCA1-positive. The LY6K-positive group had a significantly worse overall survival (OS) than the LY6K-negative group ( P  = 0.012), and the CDCA1-positive group had a significantly worse OS than the CDCA1-negative group ( P  = 0.010). A multivariate analysis suggested that pathological N stage, venous invasion, LK6Y-positive and CDCA1-positive were independent prognostic factors. The patients were classified into four groups according to the staining pattern combinations of the two CTA. The LY6K-positive and CDCA1-positive group was found to have a significantly poorer outcome than the other groups., Conclusion: ESCC patients with a combination of LY6K and CDCA1 expression in their tumor tissues had a worse prognosis than all the other ESCC patients and it was an independent factor associated with prognosis for patients with ESCC., Competing Interests: Conflicts of Interest: Authors declare no conflicts of interest for this article. Ethical Statement: The protocol for this retrospective study has been approved by the institutional review board of the Tokai University Hospital (Registration No. 13R‐058). This work followed the guidelines set forth in the Helsinki Declaration of 1975, as revised in 2000, concerning Human and Animal Rights., (© 2020 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Cancer vaccines are promising adjuvant immunotherapies that can stimulate the immune system to recognize tumor-associated antigens and eliminate the residual or recurring disease. The aberrant and restricted expression of highly immunogenic cancer testis antigen NY-ESO-1 in several malignancies, including triple-negative breast cancer, melanoma, myelomas, and ovarian cancer, makes NY-ESO-1 an attractive antigenic target for cancer vaccines. This study describes a NY-ESO-1 vaccine based on a bio-inspired nanomaterial platform technology, specifically a plant virus nanoparticle. The 30 nm icosahedral plant virus cowpea mosaic virus (CPMV) displaying multiple copies of human HLA-A2 restricted peptide antigen NY-ESO-1 157-165 exhibited enhanced uptake and activation of antigen-presenting cells and stimulated a potent CD8 + T cell response in transgenic human HLA-A2 expressing mice. CD8 + T cells from immunized mice exhibited antigen-specific proliferation and cancer cell cytotoxicity, highlighting the potential application of a CPMV-NY-ESO-1 vaccine against NY-ESO-1 + malignancies., Competing Interests: The authors declare no competing financial interest.

PRAME or PReferentially expressed Antigen in Melanoma is a testis-selective cancer testis antigen (CTA) with restricted expression in somatic tissues and re-expression in various cancers. It is one of the most widely studied CTAs and has been associated with the outcome and risk of metastasis. Although little is known about its pathophysiological function, PRAME has gained interest as a candidate target for immunotherapy. This review provides an update on our knowledge on PRAME expression and function in healthy and malignant cells and the current immunotherapeutic strategies targeting PRAME with their specific challenges and opportunities. We also highlight some of the features that position PRAME as a unique cancer testis antigen to target. [ABSTRACT FROM AUTHOR]

Melanoma-associated antigen 3 (MAGE-A3) expression is generally restricted to the placenta and germline cells of the testis, but it may also be expressed in sarcoma and other cancers and is associated with poor prognosis. Immunotherapy approaches targeting MAGE-A3 in other cancers have shown mixed results in the clinic, however, use of cancer testis antigens such as MAGE-A3 may have therapeutic value in the treatment of soft tissue sarcomas. Based on the recent success of anti-programmed death-1 (PD-1) therapy in undifferentiated pleomorphic sarcoma, we hypothesize that MAGE-A3-based immunotherapies may also provide benefits in this sarcoma type. We analyzed MAGE-A3 expression of sarcoma subtypes available in the Cancer Genome Atlas and Cancer Cell Line Encyclopedia and show that undifferentiated pleomorphic sarcoma/myxofibrosarcoma (UPS/MFS) expresses this potential target gene. We have identified high protein expression by tissue microarray of 106 UPS cores. We also found that high MAGE-A3 mRNA and protein expression is associated with worse overall survival in UPS/MFS. Furthermore, our results show no human leukocyte antigen (HLA) expression loss and relatively high lymphocyte infiltration by lymphocyte specific protein tyrosine kinase (LCK) marker expression. Based on these results, we propose targeting MAGE-A3 in UPS/MFS by immunotherapy techniques. [ABSTRACT FROM AUTHOR]

Objectives: Melanoma-associated antigen A1 (MAGEA1) is a potential target for immunotherapy and has been associated with poor survival rate in several cancers. However, little is known about the prognostic predictive value of MAGEA1 in oesophageal squamous cell carcinoma (OSCC). This study aims to determine whether the expression of MAGEA1 is an independent predictor of survival in patients with resectable OSCC., Methods: A retrospective analysis was performed on a large cohort of 197 patients with OSCC who underwent radical surgical treatment in the Department of Thoracic Surgery between January 2006 and December 2012. The expression of MAGEA1 in OSCC and matched normal oesophageal mucosa specimens from these patients was detected by immunohistochemistry with tissue microarray technology., Results: The MAGEA1 protein was expressed in the cytoplasm and nucleus of tumour cells. The positive expression rate of MAGEA1 was significantly higher in OSCC tissue than in normal oesophageal mucosa (73.6% vs 5.6%, P < 0.001). MAGEA1 expression had no correlations with sex, age, history of smoking, alcohol consumption, family history of upper gastrointestinal cancer, T stage, lymph node metastasis, grade/location of the tumour or TNM stage (all at P > 0.05). Compared with those with negative MAGEA1 expression, patients with positive MAGEA1 expression were associated with a reduced overall survival rate (5-year survival rate: 53.8% vs 37.2%; P = 0.018). The multivariable analysis revealed that MAGEA1 expression is an independent predictor of prognosis (P = 0.007, hazard ratio 1.85, 95% confidence interval 1.19-2.89)., Conclusions: The expression of MAGEA1 is abundant in Chinese patients with OSCC and is related to a worse clinical outcome. MAGEA1 may be a useful prognostic factor in patients with resectable OSCC., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)