Immune Activation and Anemia Are Associated with Decreased Quality of Life in Patients with Solid Tumors

Abstract

Anemia often coincides with depression and impaired quality of life (QoL) in cancer patients. Sustained immune activation can lead to the development of anemia. Furthermore, it also may go along with changes in tryptophan and phenylalanine metabolism. The aim of our pilot study was to study the relationship between anemia, immune-mediated changes in amino acid metabolism, and the QoL and mood of cancer patients. Questionnaires to measure QoL and depression were completed by 152 patients with solid tumors. Hemoglobin, parameters of immune activation as well as tryptophan and phenylalanine metabolism were determined in the patients’ sera. Anemic patients (51.7%) presented with higher inflammatory markers, and a higher tryptophan breakdown with lower tryptophan concentrations. They reported an impaired QoL and had higher depression scores. Patients with an impaired QoL (65.8%) also suffered from more fatigue and impaired physical, emotional, and social functioning. They, furthermore, presented with higher concentrations of inflammatory markers (C-reactive protein (CRP) and neopterin) as well as higher tryptophan degradation (in men) and higher phenylalanine concentrations (in women). Sixty-one patients (40.1%) had (mostly mild) depression. In these patients, a higher degree of Th1 immune activation was found. The results of our study suggest that cancer-related anemia goes along with an impaired QoL, which is also associated with immune-mediated disturbances of tryptophan and phenylalanine metabolism.

Physiology and Inflammation Driven Pathophysiology of Iron Homeostasis—Mechanistic Insights into Anemia of Inflammation and Its Treatment

“…IFN-γ induces neopterin production in macrophages which reflects the extent of cellular immune activation and oxidative stress, and has thus been used as a clinical marker to monitor cellular immune activation in vivo [189]. Elevated serum concentrations of neopterin were associated with a poor outcome and anemia in patients with cancer [25,190], CAD [16], CHF [191] and pulmonary disease [192,193]. IFN-γ further activates indoleamine 2,3-dioxygenase (IDO) thus promoting tryptophan breakdown [194][195][196].…”

“…Increased inflammation induced tryptophan breakdown via the kynurenine pathway reduces tryptophan availability for serotonin and melatonin synthesis, thus contributing to neurobehavioral symptoms including fatigue or depression [202,203], which are also common symptoms in patients suffering from anemia. Decreased tryptophan concentrations and increased kynurenine formation have been associated with decreased hemoglobin concentrations in patients with HIV-infection [204], with cancer [25,197] and also in patients with anemia of chronic disease [205]. Interestingly, both anemia and tryptophan catabolism correlated significantly with an impaired QoL and depression in patients with solid tumors [25].…”

“…Decreased tryptophan concentrations and increased kynurenine formation have been associated with decreased hemoglobin concentrations in patients with HIV-infection [204], with cancer [25,197] and also in patients with anemia of chronic disease [205]. Interestingly, both anemia and tryptophan catabolism correlated significantly with an impaired QoL and depression in patients with solid tumors [25]. Therefore, AI and tryptophan breakdown appear to be interconnected and might both contribute importantly to fatigue, depression and decreased QoL in patients with inflammatory disorders.…”

“…In cancer patients for instance, anemia is a common comorbidity found in approximately 40-60% of patients with malignancies mostly due to AI but often aggravated by anti-cancer therapy [27,28]. It is associated with fatigue and poor QoL [25,29] as well as impaired local tumor control [30,31]. Moreover, anemia is encountered in approximately 20% of CHF patients [32] and associated with higher NYHA classes, increased NT-proBNP concentrations and mortality [17].…”

Remodeling of metabolism and inflammation by exercise ameliorates tumor-associated anemia

“…Moreover, in response to tumor-reductive therapy, 75% of patients will develop anemia ( 1 ). Cancer-related anemia is associated with fatigue and a substantial reduction in quality of life ( 4 , 5 ) and is an independent predictor for survival ( 6 ). The current standard care for anemic patients with cancer exclusively focuses on augmenting erythropoiesis and is limited to iron supplementation, erythropoiesis-stimulating agents such as erythropoietin (EPO), or blood transfusion for patients suffering from severe anemia ( 7 ).…”