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四种癌症睾丸抗原在三阴性乳腺癌中的表达表明潜在的通用免疫治疗靶点。

Expression of four cancer-testis antigens in TNBC indicating potential universal immunotherapeutic targets.

机构信息

Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.

Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, China.

出版信息

J Cancer Res Clin Oncol. 2023 Nov;149(16):15003-15011. doi: 10.1007/s00432-023-05274-0. Epub 2023 Aug 23.

DOI:10.1007/s00432-023-05274-0
PMID:37610673
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10602960/
Abstract

OBJECTIVE

Immunotherapy is an attractive treatment for breast cancer. Cancer-testis antigens (CTAs) are potential targets for immunotherapy for their restricted expression. Here, we investigate the expression of CTAs in breast cancer and their value for prognosis. So as to hunt for a potential panel of CTAs for universal immunotherapeutic targets.

MATERIAL AND METHODS

A total of 137 breast cancer tissue specimens including 51 triple-negative breast cancer (TNBC) were assessed for MAGE-A4, MAGEA1, NY-ESO-1, KK-LC-1 and PRAME expression by immunohistochemistry. The expression of PD-L1 and TILs was also calculated and correlated with the five CTAs. Clinical data were collected to evaluate the CTA's value for prognosis. Data from the K-M plotter were used as a validation cohort.

RESULTS

The expression of MAGE-A4, NY-ESO-1 and KK-LC-1 in TNBC was significantly higher than in non-TNBC (P = 0.012, P = 0.005, P < 0.001 respectively). 76.47% of TNBC expressed at least one of the five CTAs. Patients with positive expression of either MAGE-A4 or PRAME had a significantly extended disease-free survival (DFS). Data from the Kaplan-Meier plotter confirm our findings.

CONCLUSIONS

MAGE-A4, NY-ESO-1, PRAME and KK-LC-1 are overexpressed in breast cancer, especially in TNBC. Positive expression of MAGE-A4 or PARME may be associated with prolonged DFS. A panel of CTAs is attractive universal targets for immunotherapy.

摘要

目的

免疫疗法是治疗乳腺癌的一种有吸引力的方法。肿瘤睾丸抗原（CTAs）因其表达受限，是免疫治疗的潜在靶点。在这里，我们研究了 CTAs 在乳腺癌中的表达及其对预后的价值。以便寻找潜在的 CTA 通用免疫治疗靶点。

材料和方法

通过免疫组织化学法评估了 137 例乳腺癌组织标本（包括 51 例三阴性乳腺癌（TNBC））中 MAGE-A4、MAGEA1、NY-ESO-1、KK-LC-1 和 PRAME 的表达。还计算了 PD-L1 和 TILs 的表达，并与五个 CTA 相关联。收集临床资料评估 CTA 对预后的价值。使用 K-M plotter 的数据作为验证队列。

结果

TNBC 中 MAGE-A4、NY-ESO-1 和 KK-LC-1 的表达明显高于非 TNBC（P=0.012，P=0.005，P<0.001）。76.47%的 TNBC 表达至少一种五种 CTAs 之一。MAGE-A4 或 PRAME 阳性表达的患者无病生存期（DFS）显著延长。来自 Kaplan-Meier plotter 的数据证实了我们的发现。

结论

MAGE-A4、NY-ESO-1、PRAME 和 KK-LC-1 在乳腺癌中过度表达，尤其是在 TNBC 中。MAGE-A4 或 PARME 的阳性表达可能与延长 DFS 相关。CTA 组是有吸引力的通用免疫治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c355/10602960/b60416ae9421/432_2023_5274_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c355/10602960/b6d339d11ad5/432_2023_5274_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c355/10602960/830c556da9bc/432_2023_5274_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c355/10602960/b60416ae9421/432_2023_5274_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c355/10602960/b6d339d11ad5/432_2023_5274_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c355/10602960/830c556da9bc/432_2023_5274_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c355/10602960/b60416ae9421/432_2023_5274_Fig3_HTML.jpg

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