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雄激素剥夺疗法对前列腺癌组织中PD-L1表达及免疫活性的影响

Influence of Androgen Deprivation Therapy on the PD-L1 Expression and Immune Activity in Prostate Cancer Tissue.

作者信息

Sommer Ulrich, Ebersbach Celina, Beier Alicia-Marie K, Baretton Gustavo B, Thomas Christian, Borkowetz Angelika, Erb Holger H H

机构信息

Institute of Pathology, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.

National Center for Tumor Diseases Partner Site Dresden and German Cancer Center Heidelberg, Dresden, Germany.

出版信息

Front Mol Biosci. 2022 Jun 28;9:878353. doi: 10.3389/fmolb.2022.878353. eCollection 2022.

Abstract

Immune checkpoint inhibitors have become a promising new therapy for cancer treatment. However, due to prostate cancer's high heterogeneity and immune-suppressive tumour microenvironment, clinical trials with immune checkpoint inhibitors for prostate cancer resulted in low or no response. This descriptive and retrospective study investigates the influence of androgen deprivation therapy (ADT) on PD-L1 expression and CD8 T-cell tumour infiltration and activity in primary prostate cancer tissue. Therefore, immunohistochemistry was used to assess PD-L1, CD8 T-cell, and the immune activation marker Granzyme B (GrB) in PCa tissue before and under ADT. In line with previous studies, few prostate cancer tissues showed PD-L1 expression and CD8 T-cell infiltration. However, PD-L1 expression levels on tumour cells or infiltrating immune cells above 5% generated an immune-suppressive tumour microenvironment harbouring hypofunctional CD8 T-cells. Moreover, analysis of a longitudinal patient cohort before and under ADT revealed that ADT increased hypofunctional CD8 T cells in the tumour area suggesting a tumour immune milieu optimal for targeting with immunotherapy.

摘要

免疫检查点抑制剂已成为一种很有前景的癌症治疗新方法。然而,由于前列腺癌高度异质性和免疫抑制性肿瘤微环境,免疫检查点抑制剂用于前列腺癌的临床试验反应率低或无反应。这项描述性和回顾性研究调查了雄激素剥夺疗法(ADT)对原发性前列腺癌组织中PD-L1表达、CD8 T细胞肿瘤浸润及活性的影响。因此,采用免疫组化法评估ADT治疗前及治疗期间前列腺癌组织中PD-L1、CD8 T细胞及免疫激活标志物颗粒酶B(GrB)。与之前的研究一致,很少有前列腺癌组织显示PD-L1表达和CD8 T细胞浸润。然而,肿瘤细胞或浸润免疫细胞上PD-L1表达水平高于5%会产生具有功能低下的CD8 T细胞的免疫抑制性肿瘤微环境。此外,对ADT治疗前及治疗期间患者纵向队列的分析显示,ADT增加了肿瘤区域功能低下的CD8 T细胞,提示肿瘤免疫环境有利于免疫治疗靶向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3687/9273856/2a3ef281564e/fmolb-09-878353-g001.jpg

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