Tumors and tumor resection alter circadian rhythms

Abstract

Cancer in humans alters circadian rhythms, including those of the immune system. Cancer patients display altered cortisol and immune cell rhythms, along with independent functional changes in immune cell proinflammatory cytokine responses. These altered immune/circadian effects are hypothesized to be due to cancer treatments, stress, and/or tumor physiology. Animal models indicate that tumors alone reorganize circadian metabolic control, body temperature, and corticosterone, but it is unknown whether immune rhythms are also influenced by tumors or whether potential circadian changes persist after tumor resection. This experiment tested the hypothesis that tumor resection attenuates tumor-induced alteration of circadian rhythms. Tumors were induced using non-metastatic mammary cancer cells, some were resected (“tumor-resect”) whereas others remained (“tumor”). Controls received sham surgery. Trunk blood was collected in all groups at zeitgeber time (ZT) 0, 6, 12, and 18 (n = 5–7/group/time). Whole blood was used to quantify immune populations using flow cytometry. Plasma was assessed for glucocorticoids using ELISA. Tumors increased the proportion and altered the circadian pattern of Ly6Chigh and Ly6Clow monocytes and neutrophils. Tumor resection attenuated the increased proportion of monocytes, but the dysrhythmia persisted. Tumors flattened corticosterone rhythms, which was tempered with tumor resections. Circadian rhythm behavioral data collection is underway. Taken together, persistent immune issues in survivors may be due, in part, to biological consequences of prior tumor exposure on circadian rhythms.