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Impaired Immune Health in Survivors of Diffuse Large B-Cell Lymphoma.

弥漫性大 B 细胞淋巴瘤幸存者的免疫健康受损。

  • 影响因子:11.08
  • DOI:10.1200/JCO.19.01937
  • 作者列表:"Shree T","Li Q","Glaser SL","Brunson A","Maecker HT","Haile RW","Levy R","Keegan THM
  • 发表时间:2020-02-21

PURPOSE:Therapeutic advances for diffuse large B-cell lymphoma (DLBCL) have led to an increasing number of survivors. Both DLBCL and its treatments perturb the immune system, yet little is known about immune health during extended survivorship. METHODS:In this retrospective cohort study, we compared 21,690 survivors of DLBCL from the California Cancer Registry (CCR) to survivors of breast, prostate, head and neck, and melanoma cancers. We linked their CCR records to a statewide database documenting hospital, emergency room, and ambulatory surgery visits and investigated the incidence of autoimmune conditions, immune deficiencies, and infections 1-10 years after cancer diagnosis. RESULTS:We found elevated incidence rate ratios (IRRs) for many immune-related conditions in survivors of DLBCL compared with other cancer survivors, including significantly and consistently elevated IRRs for viral and fungal pneumonias (up to 10.8-fold), meningitis (up to 5.3-fold), as well as humoral deficiency (up to 17.6-fold) and autoimmune cytopenias (up to 12-fold). IRRs for most conditions remained high even in the late survivorship period (5-10 years after cancer diagnosis). The elevated risks could not be explained by exposure to chemotherapy, stem-cell transplantation, or rituximab, except for IRRs for humoral deficiency, which were consistently higher after the incorporation of rituximab into DLBCL treatments. CONCLUSION:To our knowledge, this is the largest cohort study with extended follow-up to demonstrate impaired immune health in survivors of DLBCL. The observed persistent, elevated risks for autoimmune diseases, immune deficiencies, and infectious conditions may reflect persistent immune dysregulation caused by lymphoma or treatment and may lead to excess morbidity and mortality during survivorship. Improved understanding of these risks could meaningfully improve long-term care of patients with DLBCL.


目的: 弥漫性大 b细胞淋巴瘤 (DLBCL) 的治疗进展导致越来越多的幸存者。DLBCL 及其治疗都会扰乱免疫系统,但对长期存活期间的免疫健康知之甚少。 方法: 在这项回顾性队列研究中,我们比较了来自加州癌症登记处 (CCR) 的 21,690 例 DLBCL 幸存者与乳腺癌、前列腺癌、头颈部和黑色素瘤幸存者。我们将他们的 CCR 记录与全州范围的数据库联系起来,记录医院、急诊室和门诊手术访视,并调查癌症诊断后 1-10 年的自身免疫状况、免疫缺陷和感染的发生率。 结果: 我们发现 DLBCL 幸存者与其他癌症幸存者相比,许多免疫相关疾病的发病率比率 (irr) 升高, 包括病毒和真菌性肺炎 (高达 10.8 倍) 、脑膜炎 (高达 5.3 倍) 以及体液缺乏 (高达 17.6 倍) 的 irr 显著和持续升高和自身免疫性血细胞减少(高达 12 倍)。即使在晚期存活期 (癌症诊断后 5-10 年),大多数情况下的 irr 仍然很高。升高的风险不能通过暴露于化疗、干细胞移植或利妥昔单抗来解释,除了体液缺陷的 irr,利妥昔单抗纳入 DLBCL 治疗后,irr 一直较高。 结论: 据我们所知,这是最大的队列研究,随访时间延长,证明 DLBCL 幸存者的免疫健康受损。观察到的自身免疫性疾病、免疫缺陷和感染性疾病的持续、升高的风险可能反映了淋巴瘤或治疗引起的持续免疫失调,并可能导致生存期间的超额发病率和死亡率。提高对这些风险的认识可以有意义地改善 DLBCL 患者的长期护理。



作者列表:["Abrahamsson H","Jensen BV","Berven LL","Nielsen DL","Šaltytė Benth J","Johansen JS","Larsen FO","Johansen JS","Ree AH"]

METHODS::In colorectal cancer (CRC), hepatic arterial infusion (HAI) chemotherapy may convert primarily unresectable CRC liver metastases (CLM) into resectability, although the risk of metastatic recurrence remains high after CLM ablation. We investigated the role of antitumour immunity invoked by first-line oxaliplatin-HAI for long-term CLM outcome. In a prospective study cohort of primarily unresectable CLM, we assessed patients' fms-related tyrosine kinase 3 ligand (FLT3LG) in serum, reflecting opportune intratumoural immune activity, at baseline and following 1-3 sequences of oxaliplatin-HAI. The end points were CLM resectability and overall survival. Patients who presented an immediate twofold increment of circulating FLT3LG during the treatment and at its completion were scored as CLM resectable (16.4% with both features), were alive at final follow-up 8-12 years later. All patients experienced FLT3LG increase during the treatment course, but those who remained unresectable or had the disease converted but presented a slow and gradual FLT3LG accretion, later died of the metastatic disease. These data provide further support to our previous findings that tumour-directed immunity invoked by oxaliplatin-containing therapy predicts excellent outcome of early advanced CRC if macroscopic tumour ablation is rendered possible by the 'classic' tumour response to the cytotoxic treatment.

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作者列表:["Suvina V","Kokulnathan T","Wang TJ","Balakrishna RG"]

METHODS::Prostate cancer is one of the primary causes of death around the world. As an important drug, flutamide has been used in the clinical diagnosis of prostate cancer. However, the over dosage and improper discharge of flutamide could affect the living organism. Thus, it necessary to develop the sensor for detection of flutamide with highly sensitivity. In this paper, we report the synthesis of lanthanum cobaltite decorated halloysite nanotube (LCO/HNT) nanocomposite prepared by a facile method and evaluated for selective reduction of flutamide. The as-prepared LCO/HNT nanocomposite shows the best catalytic performance towards detection of flutamide, when compared to other bare and modified electrodes. The good electrochemical performance of the LCO/HNT nanocomposite modified electrode is ascribed to abundant active sites, large specific surface area and their synergetic effects. Furthermore, the LCO/HNT modified electrode exhibits low detection limit (0.002 μM), wide working range (0.009-145 μM) and excellent selectivity with remarkable stability. Meaningfully, the developed electrochemical sensor was applied in real environmental samples with an acceptable recovery range.

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来源期刊:Cancer letters
作者列表:["Zhou Z","Zhou Q","Wu X","Xu S","Hu X","Tao X","Li B","Peng J","Li D","Shen L","Cao Y","Yang L"]

METHODS::Several studies have indicated that cancer-associated fibroblasts (CAFs) could promote cancer progression in many malignancies. However, the mechanism by which CAFs promote the growth and metastasis of lung cancer remains poorly defined. In the present study, CAFs and normal fibroblasts (NFs) were isolated from human lung cancer and adjacent tissue. The data showed that the conditional medium (CM) of CAFs could increase the proliferation, migration and invasion of lung cancer cells. Vascular cell adhesion molecule-1 (VCAM-1) showed a higher expression in CAF-CM than NF-CM, and blocking VCAM-1 in CAF-CM attenuated the proliferation and invasion of cancer cells. Further, the results showed that VCAM-1 secreted from CAFs activated AKT and MAPK signaling via receptor α4β1 integrin (very-late antigen (VLA)-4) in lung cancer cells. Moreover, CAFs promoted VCAM-1 expression and tumor growth in vivo. Additionally, bioinformatics analysis indicated a positive correlation on the CAF marker protein alpha-smooth muscle actin (α-SMA) and VCAM-1 expression, which was associated with a poor prognosis in lung cancer patients. These findings demonstrate that the VCAM-1 secreted from CAFs enhances growth and invasion by activating the AKT and MAPK signaling of lung cancer cells.

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