Lymphocyte activation gene-3 (LAG3) mRNA and protein expression on tumour infiltrating lymphocytes (TILs) in oesophageal adenocarcinoma.
食管腺癌中淋巴细胞活化基因-3 (LAG3) mRNA和蛋白在肿瘤浸润淋巴细胞 (TILs) 上的表达。
- 作者列表："Gebauer F","Krämer M","Bruns C","Schlößer HA","Thelen M","Lohneis P","Schröder W","Zander T","Alakus H","Buettner R","Loeser H","Quaas A
PURPOSE:Lymphocyte activation gene-3 (LAG3) is an immunosuppressive checkpoint molecule expressed on T cells. The frequency and distribution of LAG3 expression in oesophageal adenocarcinoma (EAC) is unknown. Aim of the study was the evaluation and distribution of LAG3 on tumour infiltrating lymphocytes (TILs) and correlation with clinico-pathological and molecular data. METHODS:We analysed tumor tissue samples using immunohistochemistry, multi-colour immunofluorescence and mRNA in-situ technology. The analyses were performed on a multi-spot tissue microarray (TMA) with 165 samples, followed by an evaluation on a single-spot TMA with 477 samples. These results were correlated with clinical and molecular tumour data. RESULTS:LAG3 expression on TILs was detectable in 10.5% on the multi-spot TMA and 11.4% on the single-spot TMA. There was a strong correlation between protein expression and mRNA expression (p < 0.001) in TILs. LAG 3 expression was correlated with CD4+ and CD8+ T-cells within the tumor (p < 0.001). LAG3 expression showed an improved overall survival (OS) compared to patients without LAG3 expression (median OS 70.2 vs. 26.9 months; p = 0.046). The effect was even clearer in the group of patients with tumour stages > pT2 (70.2 vs 25.0 months; p = 0.037). CONCLUSION:This is the first description of LAG3 expression on TILs in EAC, underscoring the importance of immunomodulation in EAC. Our data suggest an impact of LAG3 in a relevant subset of EAC. Therapeutic studies investigating the efficacy of LAG3 inhibition in EAC will also provide predictive evidence and relevance of the immunohistochemical determination of LAG3 expression.
目的: 淋巴细胞活化基因-3 (LAG3) 是一种在T细胞上表达的免疫抑制检查点分子。LAG3在食管腺癌 (EAC) 中的表达频率和分布是未知的。本研究的目的是评估LAG3在肿瘤浸润淋巴细胞 (TILs) 上的分布以及与临床病理和分子数据的相关性。 方法: 采用免疫组织化学、多色免疫荧光和mRNA原位技术对肿瘤组织标本进行分析。在具有165个样品的多点组织微阵列 (TMA) 上进行分析，随后在具有477个样品的单点TMA上进行评估。这些结果与临床和分子肿瘤数据相关。 结果: 在多点TMA中10.5% 和在单点TMA中11.4% 可检测到til上的LAG3表达。Til中蛋白表达与mRNA表达之间存在强相关性 (p <0.001)。LAG 3表达与肿瘤内CD4 + 和CD8 + T T细胞相关 (p <0.001)。与无LAG3表达的患者相比，LAG3表达显示改善的总生存期 (OS) (中位OS 70.2个月vs. 26.9个月; P = 0.046)。在肿瘤分期> ptpt2的患者组中，效果更加明显 (70.2个月vs 25.0个月; P = 0.037)。 结论: 这是对EAC中til上LAG3表达的首次描述，强调了EAC中免疫调节的重要性。我们的数据表明LAG3在EAC的相关子集中的影响。研究在EAC中LAG3抑制的功效的治疗性研究也将提供LAG3表达的免疫组织化学测定的预测性证据和相关性。
METHODS::More than 10 years after the Centers for Disease Control and Prevention recommended routine HIV testing for patients in emergency departments (ED) and other clinical settings, as many as three out of four patients may not be offered testing, and those who are offered testing frequently decline. The current study examines how participant characteristics, including demographics and reported substance use, influence the efficacy of a video-based intervention designed to increase HIV testing among ED patients who initially declined tests offered by hospital staff. Data from three separate trials in a high volume New York City ED were merged to determine whether patients (N = 560) were more likely to test post-intervention if: (1) they resembled people who appeared onscreen in terms of gender or race; or (2) they reported problem substance use. Chi Square and logistic regression analyses indicated demographic concordance did not significantly increase likelihood of accepting an HIV test. However, participants who reported problem substance use (n = 231) were significantly more likely to test for HIV in comparison to participants who reported either no problem substance use (n = 190) or no substance use at all (n = 125) (x2 = 6.830, p < 0.05). Specifically, 36.4% of patients who reported problem substance use tested for HIV post-intervention compared to 30.5% of patients who did not report problem substance use and 28.8% of participants who did not report substance use at all. This may be an important finding because substance use, including heavy alcohol or cannabis use, can lead to behaviors that increase HIV risk, such as sex with multiple partners or decreased condom use.
METHODS::HIV self-testing has the potential to improve test access and uptake, but concerns remain regarding counselling and support during and after HIV self-testing. We investigated an oral HIV self-testing strategy together with a mobile phone/tablet application to see if and how it provided counselling and support, and how it might impact test access. This ethnographic study was nested within an ongoing observational cohort study in Cape Town, South Africa. Qualitative data was collected from study participants and study staff using 33 semi-structured interviews, one focus group discussion, and observation notes. The app provided information and guidance while also addressing privacy concerns. The flexibility and support provided by the strategy gave participants more control in choosing whom they included during testing. Accessibility concerns included smartphone access and usability issues for older and rural users. The adaptable access and support of this strategy could aid in expanding test access in South Africa.
METHODS:BACKGROUND:Several Kell-system antibodies are known to cause direct agglutination. Also, some specificities, such as anti-Ku, have been reported to react only via the indirect antiglobulin test (IAT). METHODS:Herein, we describe the case of a 61-year-old alloimmunized white woman who presented to an outside hospital with a gastrointestinal (GI) bleed and a "possible anti-Ku" was reported with 3+ reactivity at PEG-IAT and at Ficin-IAT; in addition to an unidentified cold antibody. Subsequently, when the patient presented to a second outside hospital, an anti-Ku that caused 3+ to 4+ reactions at saline-immediate spin (IS) was identified. The reactivity was evaluated with 0.01-M dithiothreitol (DTT) treatment of the plasma. RESULTS:It was determined that the strong agglutination with saline-IS was caused by immunoglobulin (Ig)M anti-Ku. CONCLUSION:To our knowledge, this is the first reported case of an IgM anti-Ku.