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对新辅助化疗有反应的乳腺癌患者中CD8 + HLA - DR + T细胞的效应机制

Effector Mechanisms of CD8+ HLA-DR+ T Cells in Breast Cancer Patients Who Respond to Neoadjuvant Chemotherapy.

作者信息

Osuna-Gómez Rubén, Arqueros Cristina, Galano Carla, Mulet Maria, Zamora Carlos, Barnadas Agustí, Vidal Silvia

机构信息

Inflammatory Diseases, Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain.

Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain.

出版信息

Cancers (Basel). 2021 Dec 7;13(24):6167. doi: 10.3390/cancers13246167.

DOI:10.3390/cancers13246167
PMID:34944786
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8699550/
Abstract

Cytotoxic T lymphocyte (CTLs) activation is an independent predictor of response to neoadjuvant chemotherapy (NACT) in breast cancer (BC) patients. Here, we go deeper into the function of CD8+ HLA-DR+ T cells from NACT treated HER2 negative BC patients. Flow cytometry analysis revealed that CD8+ HLA-DR+ T cell percentage was increased in NACT responder (R) compared to non-responder (NR) patients. R patients with ER-/PR- hormone receptors had the highest CD8+ HLA-DR+ T cell frequencies, while no differences were found when patients were classified according to cancer stage or menopause status. Interestingly, the cytotoxicity and production of anti-tumor cytokines were enhanced when CD8+ HLA-DR+ T cells from healthy donors were cultured with plasma from R, but not from NR patients. The induced anti-tumor profile of CD8+ HLA-DR+ T cells was associated with plasmatic IL-12 and IFN-γ levels, increased cytokines in R patients. IL-12 or IFN-γ neutralization decreased cytotoxic activity and TNF-α production by cultured CD8+ HLA-DR+ T cells in R plasma presence. All these data suggest that an effective response to NACT in BC patients is associated with increased IL-12 or IFN-γ levels involved in the induction of cytotoxic and pro-inflammatory mechanisms in CD8+ HLA-DR+ T cells.

摘要

细胞毒性T淋巴细胞（CTLs）激活是乳腺癌（BC）患者对新辅助化疗（NACT）反应的独立预测指标。在此，我们深入研究了接受NACT治疗的HER2阴性BC患者中CD8 + HLA-DR + T细胞的功能。流式细胞术分析显示，与无反应者（NR）患者相比，NACT反应者（R）中CD8 + HLA-DR + T细胞百分比增加。ER-/PR-激素受体的R患者具有最高的CD8 + HLA-DR + T细胞频率，而根据癌症分期或绝经状态对患者进行分类时未发现差异。有趣的是，当将健康供体的CD8 + HLA-DR + T细胞与R患者而非NR患者的血浆一起培养时，细胞毒性和抗肿瘤细胞因子的产生会增强。CD8 + HLA-DR + T细胞诱导的抗肿瘤谱与血浆IL-12和IFN-γ水平相关，R患者的细胞因子增加。IL-12或IFN-γ中和降低了在R血浆存在下培养的CD8 + HLA-DR + T细胞的细胞毒性活性和TNF-α产生。所有这些数据表明，BC患者对NACT的有效反应与参与诱导CD8 + HLA-DR + T细胞细胞毒性和促炎机制的IL-12或IFN-γ水平升高有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17be/8699550/3ed1551d8858/cancers-13-06167-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17be/8699550/83288ca50901/cancers-13-06167-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17be/8699550/7a2342dd465b/cancers-13-06167-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17be/8699550/086814a2f342/cancers-13-06167-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17be/8699550/2c043c91fbf4/cancers-13-06167-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17be/8699550/d79e4d29217c/cancers-13-06167-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17be/8699550/3ed1551d8858/cancers-13-06167-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17be/8699550/83288ca50901/cancers-13-06167-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17be/8699550/7a2342dd465b/cancers-13-06167-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17be/8699550/086814a2f342/cancers-13-06167-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17be/8699550/2c043c91fbf4/cancers-13-06167-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17be/8699550/d79e4d29217c/cancers-13-06167-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17be/8699550/3ed1551d8858/cancers-13-06167-g006.jpg

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