RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
早期乳腺癌 TIL（肿瘤浸润淋巴细胞）上免疫检查点受体 PD-1、CTLA-4、LAG-3、TIM-3 和 TIGIT 的高共表达
英文原题：High co-expression of immune checkpoint receptors PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT on tumor-infiltrating lymphocytes in early-stage breast cancer.
查看英文原题
High co-expression of immune checkpoint receptors PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT on tumor-infiltrating lymphocytes in early-stage breast cancer.
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中文摘要
肿瘤微环境中免疫检查点受体（ICR）的高表达调控抗肿瘤反应。本研究探讨了早期乳腺癌患者TIL（肿瘤浸润淋巴细胞）上ICR的差异表达。研究纳入2018年9月至2020年3月期间诊断为早期乳腺癌并接受手术的32例患者。使用MACS肿瘤分离装置和肿瘤分离试剂盒进行TIL分离。通过流式细胞术测定TIL和外周血淋巴细胞（PBL）上细胞毒性T细胞和自然杀伤（NK）细胞的PD-1、CTLA-4、LAG-3、TIM-3和TIGIT表达。Ki-67指数高、TIL密度高和HER-2阳性的患者更可能在TIL上出现CD16+CD56 dim NK细胞增加。T2肿瘤患者比T1肿瘤患者更可能在肿瘤浸润CD8+细胞毒性T细胞上出现PD-1、LAG-3和TIGIT表达增加。TIL中CD8+T和CD16-CD56 bright NK细胞的PD-1、CTLA-4、TIGIT、LAG-3和TIM-3表达彼此之间呈显著正相关。PBL和TIL中的PD1+CD8+、TIGIT+CD16+和CTLA-4+CD56+细胞呈负相关，而仅PBL和TIL中CD8+T和CD16+CD56 dim细胞的TIM-3+表达呈正相关。
我们的结果表明，TIL上的CD16+CD56 dim NK细胞可能在早期乳腺癌患者针对HER2阳性或高增殖性乳腺肿瘤的免疫反应中发挥主要作用。
此外，发现多种ICR在TIL上彼此高度共表达，包括PD-1、CTLA-4、LAG-3、TIM-3和TIGIT。这些受体可能协同抑制对肿瘤的反应，从而可能在癌变早期触发免疫逃逸机制。
然而，除TIM3外，PBLs上其他ICR的表达并未发现与其在TILs上的对应表达相伴。
展开英文摘要原文
High expression of immune checkpoint receptors (ICRs) in the tumor microenvironment regulates the anti-tumor response. In this study, the differential expressions of ICRs on tumor-infiltrating lymphocytes (TILs) in patients with early-stage breast cancer were investigated. The study included 32 patients who underwent surgery with a diagnosis of early-stage breast cancer between September 2018 and March 2020. TIL isolation was performed using a MACS tumor separation device and tumor separation kit. PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT expression of cytotoxic T and natural killer (NK) cells on TILs and peripheral blood lymphocytes (PBLs) were determined by flow cytometry.
Patients with a high Ki-67 index, high TIL density, and HER-2 positivity were more likely to have increased CD16 + CD56 dim NK cells on TILs. Patients with T2 tumors were more likely to have increased expression of PD-1, LAG-3, and TIGIT on tumor-infiltrating CD8 + cytotoxic T cells than those with T1 tumors.
PD-1, CTLA-4, TIGIT, LAG-3, and TIM-3 expression of CD8 + T and CD16 - CD56 bright NK cells in TILs showed significant positive correlations with each other. PD1 + CD8 + , TIGIT + CD16 + , and CTLA-4 + CD56 + cells in PBLs and TILs were found to be negatively correlated, whereas only TIM-3 + expression of CD8 + T and CD16 + CD56 dim cells in PBLs and TILs showed positive correlations.
Our results suggest that CD16 + CD56 dim NK cells on TILs may play a major role in the immune response against HER2-positive or highly proliferating breast tumors in patients with early-stage breast cancer.
Furthermore, various ICRs were found to be highly co-expressed with each other on TILs, including PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT. These receptors may synergistically suppress the response to the tumor, which may trigger immune escape mechanisms in the early stage of carcinogenesis.
However, ICR expressions other than TIM3 on PBLs were not found to accompany their counterparts on TILs.
论文信息
- 作者
- Mollavelioglu B、Cetin Aktas E、Cabioglu N、Abbasov A、Onder S、Emiroglu S、Tükenmez M、Muslumanoglu M
- 第一作者单位
- Istanbul Faculty of Medicine, Department of General Surgery, Istanbul University, Istanbul, Turkey.Turkey
- 通讯作者单位
- Istanbul Faculty of Medicine, Department of General Surgery, Istanbul University, Istanbul, Turkey. vozmen@istanbul.edu.tr.Turkey
- 期刊
- World journal of surgical oncology2022 Oct 21
- 原文标识
- PubMed 36271406 · DOI 10.1186/s12957-022-02810-z
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