癌睾丸抗原在犬黑色素瘤和健康组织中的表达

IF 1.4 3区农林科学 Q4 IMMUNOLOGY

Veterinary immunology and immunopathology Pub Date : 2025-05-06 DOI:10.1016/j.vetimm.2025.110946

Esther Hindriks , Wilhelmina Bergmann , Aitor Martínez Ruiz , Raffaella De Maria , Maurice M.J.M. Zandvliet , Alice J.A.M. Sijts , Femke Broere

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引用次数: 0

摘要

睾丸癌抗原（cta）是免疫肿瘤治疗的重要靶点。它们提供了治疗缺乏有效全身治疗的癌症的潜力，包括犬恶性黑色素瘤（CMM）。在这项研究中，我们研究了人类cta的8个犬同源物作为免疫治疗靶点的适宜性，包括癌症相关基因1 （CAGE1）、ccctc结合因子（CTCFL）、死盒解旋酶53 （DDX53）、黑色素瘤抗原基因（MAGE）、5′-核苷酸酶、细胞质IB （NT5C1B）、P抗原家族成员3-like （PAGE3-like）、黑色素瘤优先表达抗原（PRAME）和滑膜肉瘤X染色体断点（SSX）。免疫组织化学在12.1% %（4/33）的CMM病例中检测到MAGE蛋白，包括手指和口腔黑色素瘤，健康组织表达仅限于睾丸。采用Real-time PCR检测犬睾丸中CTA mRNA，并通过凝胶电泳和Sanger测序进行验证。MAGE、PAGE3-like和PRAME mRNA在犬口腔黑色素瘤和转移细胞系中强烈表达，在正常组织中表达受限。CAGE1、CTCFL、DDX53和SSX6在犬口腔黑色素瘤中仅弱表达或不表达。CTCFL和DDX53在健康组织中的表达并不局限于睾丸，在肾脏中也有中度表达。这些结果表明狗表达cta，与人类相似，因此cta可以作为狗免疫治疗的靶点。

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Cancer-testis antigen expression in canine melanoma and healthy tissues

Cancer-testis antigens (CTAs) are promising targets for immuno-oncotherapy. They offer the potential to treat cancers for which effective systemic therapies are lacking, including canine malignant melanoma (CMM). In this study, we investigate the suitability of eight canine orthologs of human CTAs as targets for immunotherapy, including cancer-associated gene 1 (CAGE1), CCCTC-binding factor (CTCFL), DEAD-box helicase 53 (DDX53), the melanoma antigen gene (MAGE), 5′-nucleotidase, cytosolic IB (NT5C1B), P antigen family member 3-like (PAGE3-like), preferentially expressed antigen in melanoma (PRAME), and synovial sarcoma X chromosome breakpoint (SSX). MAGE proteins were detected by immunohistochemistry in 12.1 % (4/33) of CMM cases, including digital and oral melanoma, with healthy tissue expression restricted to the testis. CTA mRNA was detected by Real-time PCR in canine testis and validated through gel electrophoresis and Sanger sequencing. MAGE, PAGE3-like, and PRAME mRNA were strongly expressed in canine oral melanoma and metastatic cell lines with restricted expression in normal tissues. CAGE1, CTCFL, DDX53, and SSX6 were only weakly expressed or absent in canine oral melanoma. CTCFL and DDX53 expression in healthy tissues was not restricted to the testis, as moderate expression was found in the kidney. These results suggest that dogs express CTAs, similar to humans, and thus CTAs may serve as a target for immunotherapy in dogs.

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来源期刊

Veterinary immunology and immunopathology 农林科学-免疫学

CiteScore

3.40

自引率

5.60%

发文量

审稿时长

70 days

期刊介绍： The journal reports basic, comparative and clinical immunology as they pertain to the animal species designated here: livestock, poultry, and fish species that are major food animals and companion animals such as cats, dogs, horses and camels, and wildlife species that act as reservoirs for food, companion or human infectious diseases, or as models for human disease. Rodent models of infectious diseases that are of importance in the animal species indicated above,when the disease requires a level of containment that is not readily available for larger animal experimentation (ABSL3), will be considered. Papers on rabbits, lizards, guinea pigs, badgers, armadillos, elephants, antelope, and buffalo will be reviewed if the research advances our fundamental understanding of immunology, or if they act as a reservoir of infectious disease for the primary animal species designated above, or for humans. Manuscripts employing other species will be reviewed if justified as fitting into the categories above. The following topics are appropriate: biology of cells and mechanisms of the immune system, immunochemistry, immunodeficiencies, immunodiagnosis, immunogenetics, immunopathology, immunology of infectious disease and tumors, immunoprophylaxis including vaccine development and delivery, immunological aspects of pregnancy including passive immunity, autoimmuity, neuroimmunology, and transplanatation immunology. Manuscripts that describe new genes and development of tools such as monoclonal antibodies are also of interest when part of a larger biological study. Studies employing extracts or constituents (plant extracts, feed additives or microbiome) must be sufficiently defined to be reproduced in other laboratories and also provide evidence for possible mechanisms and not simply show an effect on the immune system.