关键词: B cells cancer dermatomyositis follicular dendritic cells follicular helper T cell myositis tertiary lymphoid structure tumor-infiltrating lymphocyte

来  源:   DOI:10.3389/fmed.2022.1066858   PDF(Pubmed)

Abstract:
UNASSIGNED: To investigate histologic features of immunological components in the primary tumor site of patients with cancer-associated myositis (CAM) by focusing on tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs), which play major roles in antitumor immunity.
UNASSIGNED: Cancer-associated myositis patients were selected from the single-center idiopathic inflammatory myopathy cohort based on the availability of primary tumor specimens obtained before the introduction of immunomodulatory agents. Control cancer subjects without CAM were selected from the cancer tissue repository at a ratio of 1:2 matched for demographics and cancer characteristics of CAM cases. A series of immunohistochemical analyses was conducted using sequential tumor sections. TLS was defined as an ectopic lymphoid-like structure composed of DC-LAMP+ mature dendritic cells, CD23+ follicular dendritic cells (FDCs) and PNAd+ high endothelial venules. TLS distribution was classified into the tumor center, invasive margin, and peritumoral area.
UNASSIGNED: Six CAM patients and 12 matched non-CAM controls were eligible for the study. There was no apparent difference in the density or distribution of TILs between the groups. TLSs were found in 3 CAM patients (50%) and 4 non-CAM controls (33%). TLSs were exclusively located at the tumor center or invasive margin in CAM cases but were mainly found in the peritumoral area in non-CAM controls. FDCs and class-switched B cells colocalized with follicular helper T cells were abundantly found in the germinal center-like area of TLSs from CAM patients compared with those from non-CAM controls.
UNASSIGNED: The adaptive immune response within TLSs in the primary tumor site might contribute to the pathogenic process of CAM.
摘要:
未经证实:通过关注肿瘤浸润性淋巴细胞(TIL)和三级淋巴结构(TLS),研究癌症相关肌炎(CAM)患者原发肿瘤部位免疫成分的组织学特征,在抗肿瘤免疫中起主要作用。
UNASSIGNED:根据在引入免疫调节剂之前获得的原发肿瘤标本的可用性,从单中心特发性炎症性肌病队列中选择癌症相关肌炎患者。没有CAM的对照癌症受试者以1:2的比例从癌症组织库中选择,匹配CAM病例的人口统计学和癌症特征。使用连续的肿瘤切片进行一系列免疫组织化学分析。TLS被定义为由DC-LAMP+成熟树突状细胞组成的异位淋巴样结构,CD23+滤泡树突状细胞(FDCs)和PNAd+高内皮小静脉。TLS分布被分类到肿瘤中心,侵入性边缘,和肿瘤周围区域。
UNASSIGNED:6名CAM患者和12名匹配的非CAM对照者符合研究条件。两组之间TIL的密度或分布没有明显差异。在3例CAM患者(50%)和4例非CAM对照(33%)中发现了TLS。在CAM病例中,TLS仅位于肿瘤中心或浸润性边缘,但主要在非CAM对照的肿瘤周围区域发现。与非CAM对照组相比,在CAM患者的TLS的生发中心样区域中大量发现了与滤泡辅助性T细胞共定位的FDC和类别转换B细胞。
UNASSIGNED:原发肿瘤部位TLS内的适应性免疫反应可能与CAM的致病过程有关。
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