器官特异性免疫设定点是乳腺癌不同转移部位免疫特征差异的基础。

IF 8.1 1区 医学 Q1 IMMUNOLOGY
Colt A Egelston, Weihua Guo, Diana L Simons, Jian Ye, Christian Avalos, Shawn T Solomon, Mary Nwangwu, Michael S Nelson, Jiayi Tan, Eliza R Bacon, Kena Ihle, Daniel Schmolze, Lusine Tumyan, James R Waisman, Peter P Lee
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引用次数: 0

摘要

肿瘤微环境(TME)中的免疫组成对癌症的转移倾向和治疗反应起着核心作用。以前的研究表明,转移性肿瘤微环境受到免疫抑制。然而,由于患者体内多个转移部位的可及性有限,因此很难对多器官转移情况下的免疫TME进行评估。我们利用快速尸检组织收集方案来评估乳腺癌转移灶多个部位和配对无肿瘤组织中的免疫组成。结果发现,转移灶的免疫细胞密度和组成与相同器官类型的配对无瘤组织相当。相比之下,转移组织和无肿瘤组织中的免疫细胞密度在器官类型之间存在显著差异,肺部的免疫浸润始终大于肝脏。这些免疫分析结果与流式细胞术和基于多重免疫荧光的空间分析结果一致。此外,我们还发现粒细胞是肺转移灶和肝转移灶中最主要的肿瘤浸润免疫细胞,而且这些粒细胞在许多组织部位的 PD-L1 表达细胞中占多数。我们还发现了肺转移瘤和肝转移瘤中不同的潜在免疫抑制机制,肺转移瘤中 PD-L1+ 抗原递呈细胞表达增加,而肝转移瘤中活化的调节性 T 细胞和 HLA-DR 低单核细胞数量较多。这些结果共同表明,转移瘤的免疫环境是由器官类型决定的,免疫疗法策略可能会受益于针对免疫TME组织特异性特征的独特定制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Organ-Specific Immune Setpoints Underlie Divergent Immune Profiles across Metastatic Sites in Breast Cancer.

Immune composition within the tumor microenvironment (TME) plays a central role in the propensity of cancer cells to metastasize and respond to therapy. Previous studies have suggested that the metastatic TME is immune-suppressed. However, limited accessibility to multiple metastatic sites within patients has made assessing the immune TME difficult in the context of multiorgan metastases. We utilized a rapid postmortem tissue collection protocol to assess the immune composition of numerous sites of breast cancer metastasis and paired tumor-free tissues. Metastases had comparable immune cell densities and compositions to paired tumor-free tissues of the same organ type. In contrast, immune cell densities in both metastatic and tumor-free tissues differed significantly between organ types, with lung immune infiltration being consistently greater than that in the liver. These immune profiling results were consistent between flow cytometry and multiplex immunofluorescence-based spatial analysis. Furthermore, we found that granulocytes were the predominant tumor-infiltrating immune cells in lung and liver metastases, and these granulocytes comprised most PD-L1-expressing cells in many tissue sites. We also identified distinct potential mechanisms of immunosuppression in lung and liver metastases, with the lung having increased expression of PD-L1+ antigen-presenting cells and the liver having higher numbers of activated regulatory T cells and HLA-DRlow monocytes. Together, these results demonstrate that the immune contexture of metastases is dictated by organ type and that immunotherapy strategies may benefit from unique tailoring to the tissue-specific features of the immune TME.

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来源期刊
Cancer immunology research
Cancer immunology research ONCOLOGY-IMMUNOLOGY
CiteScore
15.60
自引率
1.00%
发文量
260
期刊介绍: Cancer Immunology Research publishes exceptional original articles showcasing significant breakthroughs across the spectrum of cancer immunology. From fundamental inquiries into host-tumor interactions to developmental therapeutics, early translational studies, and comprehensive analyses of late-stage clinical trials, the journal provides a comprehensive view of the discipline. In addition to original research, the journal features reviews and opinion pieces of broad significance, fostering cross-disciplinary collaboration within the cancer research community. Serving as a premier resource for immunology knowledge in cancer research, the journal drives deeper insights into the host-tumor relationship, potent cancer treatments, and enhanced clinical outcomes. Key areas of interest include endogenous antitumor immunity, tumor-promoting inflammation, cancer antigens, vaccines, antibodies, cellular therapy, cytokines, immune regulation, immune suppression, immunomodulatory effects of cancer treatment, emerging technologies, and insightful clinical investigations with immunological implications.
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