Understanding Psychosocial and Immunologic Responses in Indolent Lymphoproliferative Disorders

了解惰性淋巴细胞增殖性疾病的心理社会和免疫反应

• 批准号: 9038558
• 负责人: Kerry S Campbell
• 金额: $ 66.25万
• 依托单位: RESEARCH INST OF FOX CHASE CAN CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9038558
• 关键词: Activated Natural Killer Cell; Adverse effects; Affect; Affective; Anxiety; Appointment; Arousal; Biological Markers; Cancer Model; Cancer Patient; Cell physiology; Characteristics; Classification; Clinical; Development; Diagnosis; Disease; Disease Progression; Disease model; Distress; Early identification; Flow Cytometry; Follicular Lymphoma; Fright; Future; Health Care Costs; Human; Immune; Immune response; Immunity; Immunologic Markers; Immunologics; Individual; Individual Differences; Indolent; Lead; Life; Longitudinal Studies; Lymphocyte; Lymphoproliferative Disorders; Malignant Neoplasms; Monitor; Morbidity - disease rate; NK Cell Activation; Natural Killer Cells; Neurotic Disorders; Newly Diagnosed; Non-Hodgkin' s Lymphoma; Outcome; Pathway interactions; Patient Monitoring; Patients; Personal Satisfaction; Phase; Phenotype; Physiological; Play; Psychological Stress; Reporting; Research; Risk; Risk Factors; Role; Stress; Sum; Symptoms; T-Cell Activation; T-Lymphocyte; Time; Uncertainty; animal data; biobehavior; biological adaptation to stress; cancer therapy; clinically relevant; exhaust; exhaustion; experience; immune function; killer T cell; large cell Diffuse non-Hodgkin' s lymphoma; novel; optimism; patient population; prognostic; prospective; psychologic; psychosocial; public health relevance; receptor; response; standard of care; stressor; time interval; tool; tumor progression

 DESCRIPTION (provided by applicant): In 2015, about 71,850 cases of non-Hodgkin lymphoma [NHL] will be diagnosed in the US. Approximately 35% of patients with NHL will present with indolent disease, which progresses very slowly, but is considered incurable. Because there is no survival benefit to initiating treatment immediately after diagnosis, a "watch-and- wait" [WW] approach (in which patients are monitored frequently) is the standard of care until disease-related symptoms emerge. The benefits of WW include reduced healthcare costs and avoidance of treatment-related side effects; however, many patients report elevated levels of distress and cancer-related worry during the WW phase. The uncertainty associated with the unknown trajectory of an incurable disease can be distressing and act as a powerful stressor, resulting in both psychological and physiological consequences. Notably, some individuals may be more affected by uncertain situations. Individual differences in various characteristics, such as "intolerance of uncertainty" [IU] and neuroticism, have been associated with greater stress and physiologic arousal. Over time, stress-related immune alterations may have clinical consequences for disease progression, since immune deficits are a strong risk factor for NHL. Natural killer [NK] cells, which are particularly sensitive to psychological stress, are critical i controlling NHL. In humans, lower numbers of NK cells, reduced viability of NK cells, and diminished expression of NK cell activating receptors have been associated with NHL disease progression and shorter survival, whereas stronger host immunity is associated with a more indolent disease course. T cells are also key effectors in mounting immune responses to NHL, and through the use of modern flow cytometry, their biomarker phenotypes can now provide sensitive indicators of immune function. Given the anxiety and distress associated with a WW approach, and the role of immune factors in disease progression, indolent NHL offers a unique disease model within which to examine biobehavioral pathways in an untreated cancer patient population. Thus, guided by a biobehavioral model of cancer stress, we propose to conduct a prospective, longitudinal study of 225 newly diagnosed patients with indolent NHL undergoing WW, to investigate whether poorer psychosocial functioning (as characterized by higher stress and anxiety) is associated with suppressed NK functional activity (degranulation response) and reduced expression of activating NK cell receptors, which in turn, have prognostic implications for disease progression over time. The specific aims are: Aim 1. To examine associations of psychosocial functioning (e.g., perceived stress, anxiety) with expression of NK cell and T cell activation markers and functional activity over time; Aim 2. To assess whether these immunologic markers are associated with a shorter interval of time to treatment; and Aim 3. To identify characteristics that may predict poorer outcomes over time. Study findings will have direct translational relevance, including a potential for early identification of patients at-risk or disease progression and the development of non-pharmacologic approaches for reducing morbidity in this understudied patient population.

 描述（由适用提供）：2015年，将在美国诊断出约71,850例非霍奇金淋巴瘤[NHL]。大约35％的NHL患者会出现懒惰的疾病，该疾病的进展非常缓慢，但被认为是无法治愈的。由于在诊断后立即开始治疗没有生存益处，因此（经常监测患者）是护理标准，直到出现与疾病相关的症状为止。 WW的好处包括降低医疗保健成本和避免与治疗相关的副作用；但是，许多患者报告说，在WW阶段，困扰和与癌症相关的担忧升高。与无法治愈的疾病的未知轨迹相关的不确定性可能是令人痛苦的，并充当强大的压力源，导致心理和身体后果。值得注意的是，有些人可能会受到不确定情况的影响。各种特征上的个体差异，例如“不确定性的插入率”和神经质，与更大的压力和身体唤醒有关。随着时间的流逝，与压力相关的免疫改变可能会对疾病进展产生临床后果，因为免疫障碍是NHL的强大危险因素。对心理压力特别敏感的天然杀手[NK]细胞对NHL的控制至关重要。在人类中，NK细胞数量较低，NK细胞的生存能力降低以及NK细胞激活受体的表达降低与NHL疾病的进展和较短的生存有关，而较强的宿主免疫组织化合物与更加顽强的疾病病程有关。 T细胞也是安装对NHL免疫反应的关键作用，通过使用现代流式细胞仪，它们的生物标志物表型现在可以提供免疫功能的敏感指标。鉴于与WW方法相关的焦虑和困扰，以及免疫因素在疾病进展中的作用，懒惰的NHL提供了独特的疾病模型，在该模型中，可以在未经治疗的癌症患者人群中检查生物行为途径。在癌症压力的生物行为模型的指导下，我们建议对225例新诊断的NHL进行WW进行的前瞻性，纵向研究，以调查较差的心理社会功能（由较高的压力和焦虑表征）是否与抑制的NK功能相关（DECRANTAIMENT COMPLITION nk的表达），使NK的表达与AICTIAS的表达相关，并与AICTIAS相同，使NK的表现相关，并降低了AICTIATS的疾病。 随着时间的推移。具体目的是：目标1。检查社会心理功能（例如，感知的压力，焦虑）与NK细胞和T细胞激活标记的表达以及随时间推移的功能活性的关联；目标2。评估这些免疫标记是否与较短的治疗时间间隔相关；目标3。确定可能会随着时间的推移预测结果较差的特征。研究发现将具有直接的转化相关性，包括可能早期鉴定患者处于危险或疾病进展的可能性，以及开发非药理学方法，以降低这一可理解的患者人群的发病率。