Poor Prognosis and Therapeutic Responses in LILRB1-Expressing M2 Macrophages-Enriched Gastric Cancer Patients.
Poor Prognosis and Therapeutic Responses in LILRB1-Expressing M2 Macrophages-Enriched Gastric Cancer Patients.
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表达 LILRB1 且富含 M2 巨噬细胞的胃癌患者预后不良且治疗反应不佳
DOI：
10.3389/fonc.2021.668707
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发表时间：
2021
影响因子：
4.7
通讯作者：
He Y
中科院分区：
文献类型：
--
作者：
Zhang Y;Wang H;Xu X;Liu H;Hao T;Yin S;Zhang C;He Y
免疫抑制分子是不同癌症类型有价值的预后生物标志物。白细胞免疫球蛋白样受体亚家族B1（白细胞免疫球蛋白样受体亚家族B1， LILRB1）被认为是一种免疫抑制分子，是人白细胞抗原g的重要受体。然而，LILRB1在胃癌中表达的临床意义尚不明确。我们分析了166例胃癌患者的免疫组化数据，以确定LILRB1的临床病理和生存意义。采用免疫荧光法检测LILRB1与浸润性免疫细胞的共定位。此外，我们还评估了与LILRB1相关的免疫环境、免疫细胞功能和肿瘤微环境状态。我们发现LILRB1主要存在于肿瘤间质中，肿瘤组织中LILRB1的表达高于匹配的邻近组织。lilrb1高表达与肿瘤分期越晚期、复发风险越高、生存期越差相关。免疫组织化学和生物信息学分析显示，LILRB1与M2肿瘤相关巨噬细胞（tam）浸润呈显著正相关。免疫荧光证实M2 tam是表达LILRB1的原代免疫细胞。LILRB1+ M2 tam的密集浸润产生了免疫抑制微环境，表现为CD8+ T细胞的富集和免疫抑制细胞因子的增加。此外，LILRB1+细胞和M2 tam均高浸润的患者预后较差，对辅助化疗的治疗反应性较差。总之，LILRB1+ M2 tam与促肿瘤免疫环境相关，并决定了胃癌的不良预后。进一步的研究是必要的，以探索治疗靶向LILRB1+ M2 tam。
Immunosuppressive molecules are valuable prognostic biomarkers across different cancer types. Leukocyte immunoglobulin like receptor subfamily B1 (LILRB1) is considered to be an immunosuppressive molecule, which is an important receptor of human leukocyte antigen G. However, the clinical significance of LILRB1 expression in gastric cancer remains unexplored. We analyzed the immunohistochemistry data of 166 gastric cancer patients to determine the clinicopathologic and survival significance of LILRB1. Immunofluorescence was conducted to detect the co-localization of LILRB1 with infiltrating immune cells. Additionally, we also assessed the immune contexture, immune cell functions and tumor microenvironment state related to LILRB1. We found that LILRB1 was mainly present in tumor stroma which was higher in tumor tissues compared with matched adjacent tissues. High-LILRB1 expression was associated with more advanced tumor stage, higher recurrence risk and worse survival. Immunohistochemistry and bioinformatic analysis showed that LILRB1 had a significant positive correlation with M2 tumor-associated macrophages (TAMs) infiltration. Immunofluorescence confirmed that M2 TAMs were the primary immune cells expressing LILRB1. Dense infiltration of LILRB1+ M2 TAMs yielded an immunosuppressive microenvironment manifested as enriched exhausted CD8+ T cells and increased immunosuppressive cytokines. Moreover, patients with high infiltration of both LILRB1+ cells and M2 TAMs indicated poor prognosis and inferior therapeutic responsiveness to adjuvant chemotherapy. In conclusion, LILRB1+ M2 TAMs were associated with a pro-tumor immune contexture and determine poor prognosis in gastric cancer. Further studies are essential to explore therapeutic targeting LILRB1+ M2 TAMs.
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影响因子：
10.1
作者：
Dumont, Clement;Jacquier, Alix;LeMaoult, Joel
通讯作者：
LeMaoult, Joel
影响因子：
11.5
作者：
Barros, Mario Henrique M.;Hassan, Rocio;Niedobitek, Gerald
通讯作者：
Niedobitek, Gerald
影响因子：
50.3
作者：
Ruffell B;Coussens LM
通讯作者：
Coussens LM
DOI：
10.1007/s00262-017-2023-x
发表时间：
2017-08
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
van der Touw W;Chen HM;Pan PY;Chen SH
通讯作者：
Chen SH
影响因子：
32.4
作者：
Noy, Roy;Pollard, Jeffrey W.
通讯作者：
Pollard, Jeffrey W.