Visualization of PD-L1-positive and PD-1-positive immune cell contact in the breast cancer microenvironment

Q4 Medicine
A. Kalinchuk, V. Perelmuter, L. Tashireva
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引用次数: 0

Abstract

Functioning of the Pd-1/Pd-L1 immune checkpoint in the microenvironment of breast cancer may lead to the tumor escape from the immune response. However, it is unknown how often Pd-L1 binds to Pd-1 in breast cancer patients, which Pd-L1-positive cells are predominantly involved in the interaction, and what prognostic significance it has. The objective of the study was to assess the frequency of co-location of Pd-1/Pd-L1-positive cells in the microenvironment of breast cancer as well as to determine the population of these cells. Material and Methods. The study included 25 patients with invasive breast carcinoma. Interaction between cells carrying the Pd-1 receptor and the Pd-L1 ligand in the tumor microenvironment were visualized using multiplex TSA (tyramide signal amplification)-modified immunohistochemistry. Participation of M1 macrophages (Cd68+Cd163-Cd3-CKAE1/3-), M2 macrophages (Cd68+/-Cd163+Cd3-CKAE1/3-), lymphocytes (Cd68-Cd163-Cd3+CKAE1/3-) and other immune cells in these interactions was assessed. Results. Half of the breast cancer patients included in the study had interactions of immune cells of the microenvironment, one of which carried Pd-1, and the other carried Pd-L1. The contact of cells carrying Pd-1 and Pd-L1 was associated with the level of TILs and the ratio of Pd-1+/ Pd-L1+ cells in the tumor microenvironment. The Pd-1/Pd-L1 interaction was found with similar frequency in Pd-L1 positive and negative patients. In the cell contacts, macrophages acted as Pd-L1+ cells in the vast majority of cases. Lymphocytes were Pd-1-positive cells rather than Pd-L1-carrying cells. In addition, it was found that metastasis-free survival was not associated with the presence or absence of co-localized cells carrying Pd-1 and Pd-L1 in the tumor microenvironment. Conclusion. Co-location of immune cells carrying Pd-1 and Pd-L1 occurs in breast cancer. M1 and M2 macrophages, Cd3+ lymphocytes and other immune cells are involved in these interactions. However, further studies are needed to establish the prognostic significance of these contacts.
乳腺癌微环境中 PD-L1 阳性和 PD-1 阳性免疫细胞接触可视化
乳腺癌微环境中Pd-1/Pd-L1免疫检查点的功能可能导致肿瘤逃避免疫反应。然而,目前还不清楚乳腺癌患者体内 Pd-L1 与 Pd-1 结合的频率、哪些 Pd-L1 阳性细胞主要参与了这种相互作用以及这种相互作用对预后有何意义。本研究旨在评估乳腺癌微环境中 Pd-1/Pd-L1 阳性细胞共定位的频率,并确定这些细胞的群体。材料与方法。研究对象包括 25 名浸润性乳腺癌患者。使用多重 TSA(酪胺信号放大)修饰免疫组化技术观察肿瘤微环境中携带 Pd-1 受体的细胞与 Pd-L1 配体之间的相互作用。对参与这些相互作用的 M1 巨噬细胞(Cd68+Cd163-Cd3-CKAE1/3-)、M2 巨噬细胞(Cd68+/-Cd163+Cd3-CKAE1/3-)、淋巴细胞(Cd68-Cd163-Cd3+CKAE1/3-)和其他免疫细胞进行了评估。结果研究中一半的乳腺癌患者与微环境中的免疫细胞发生了相互作用,其中一个携带 Pd-1,另一个携带 Pd-L1。携带 Pd-1 和 Pd-L1 的细胞的接触与肿瘤微环境中 TIL 的水平和 Pd-1+/ Pd-L1+ 细胞的比例有关。Pd-1/Pd-L1相互作用在Pd-L1阳性和阴性患者中出现的频率相似。在细胞接触中,绝大多数情况下巨噬细胞是 Pd-L1+ 细胞。淋巴细胞是 Pd-1 阳性细胞,而不是携带 Pd-L1 的细胞。此外,研究还发现,无转移生存期与肿瘤微环境中是否存在携带 Pd-1 和 Pd-L1 的共定位细胞无关。结论乳腺癌中存在携带 Pd-1 和 Pd-L1 的免疫细胞共定位现象。M1 和 M2 巨噬细胞、Cd3+ 淋巴细胞和其他免疫细胞参与了这些相互作用。然而,要确定这些接触的预后意义,还需要进一步的研究。
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来源期刊
Siberian journal of oncology
Siberian journal of oncology Medicine-Oncology
CiteScore
0.40
自引率
0.00%
发文量
117
审稿时长
8 weeks
期刊介绍: The main objectives of the journal are: -to promote the establishment of Russia’s leading worldwide positions in the field of experimental and clinical oncology- to create the international discussion platform intended to cover all aspects of basic and clinical cancer research, including carcinogenesis, molecular biology, epidemiology, cancer prevention, diagnosis and multimodality treatment (surgery, chemotherapy, radiation therapy, hormone therapy), anesthetic management, medical and social rehabilitation, palliative care as well as the improvement of life quality of cancer patients- to encourage promising young scientists to be actively involved in cancer research programs- to provide a platform for researches and doctors all over the world to promote, share, and discuss various new issues and developments in cancer related problems. (to create a communication platform for the expansion of cooperation between Russian and foreign professional associations).- to provide the information about the latest worldwide achievements in different fields of oncology The most important tasks of the journal are: -to encourage scientists to publish their research results- to offer a forum for active discussion on topics of major interest - to invite the most prominent Russian and foreign authors to share their latest research findings with cancer research community- to promote the exchange of research information, clinical experience, current trends and the recent developments in the field of oncology as well as to review interesting cases encountered by colleagues all over the world- to expand the editorial board and reviewers with the involvement of well-known Russian and foreign experts- to provide open access to full text articles- to include the journal into the international database- to increase the journal’s impact factor- to promote the journal to the International and Russian markets
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