Immunological and psychosocial functioning in parents of children with cancer.

PURPOSE: Research has shown that parents of children with cancer exhibit an altered immune profile compared to parents of healthy children, reflective of increased susceptibility to illness. These parents are also at risk for poorer psychosocial outcomes and quality of life. The current study compares peripheral blood cell analyses and psychosocial self-reports from parents of children being treated for cancer (n = 21) to parents of healthy children (n = 30). METHODS: A blood sample was drawn from parents to analyze immune profiles. Parents also completed the Perceived Stress Scale (PSS), Medical Outcomes Study Short Form-36 (MOS), and Patient-Reported Outcomes Measurement Information System Short Form v1.0 Emotional Distress-Anxiety 8a, and Emotional Distress-Depression 8a (PROMIS). Mann-Whitney U tests and independent samples t-tests were conducted to examine differences in outcomes between parent groups. RESULTS: Parents of children with cancer exhibited higher monocyte percentages in their peripheral blood compared to peers with healthy children. Parents of children with cancer also reported poorer psychosocial outcomes: higher perceived stress, higher anxiety and depression symptoms, more role disability resulting from emotional problems, poorer general and mental health, and poorer social functioning. CONCLUSION: These findings support research that has shown a direct effect of chronic stress on the immune system. Symptoms reported by parents of children with cancer indicate unmet psychosocial needs that could potentially affect long-term health. Given the central role of parents in their children's cancer care, it is compelling to address and work to improve parent immunological and psychosocial well-being.

Targeting TLR-4 with a novel pharmaceutical grade plant derived agonist, Immunomax®, as a therapeutic strategy for metastatic breast cancer.

BACKGROUND: Previously we demonstrated that the resection of primary 4T1 tumors only slightly prolongs mouse survival, but importantly, creates a "window of opportunity" with attenuated suppressor cell and increased activated T cell populations. This suggests that additional activation of the immune system by immunostimulatory agents during this period may enhance anti-tumor immunity and potentially eradicate micro-metastatic disease in this stringent model. We hypothesized that the immunostimulator Immunomax®, which is comprised of a plant-derived polysaccharide, is non-toxic in humans and stimulates immune defense during the infectious diseases treatment, may have also anti-tumor activity and be beneficial in the adjuvant setting when endogenous anti-tumor responses are present and during the "window of opportunity" in post-resection metastatic breast cancer model. Here we provide the initial report that Immunomax® demonstrates the capacity to eliminate micro-metastatic disease in the post-resection, 4T1 mouse model of breast cancer. METHODS: The efficacy of Immunomax® was evaluated by analyzing survival rate and the number of spontaneous clonogenic tumor cells in the lung homogenates of mice. The frequencies of activated NK, CD4(+) and CD8(+) cells as well as myeloid-derived suppressor cells and Treg cells were evaluated using flow cytometry. Highly purified mouse and human dendritic and NK cells were sorted and the effect of Immunomax® on activation status of these cells was assessed by flow cytometry. The property of Immunomax® as TLR-4 agonist was determined by NF-κB/SEAP reporter gene assay, WB, RT-PCR. RESULTS: Immunomax® injections significantly prolonged overall survival and cured 31% of mice. This immunostimulator activates DCs via the TLR-4, which in turn stimulates tumoricidal NK cells and in vitro, completely inhibits growth of 4T1 cells. Incubation of PBMC from healthy donors with Immunomax® activates NK cells via activation of plasmacytoid DC leading significantly higher efficacy in killing of human NK-target cells K562 compared with non-treated cells. CONCLUSION: This is the first demonstration that Immunomax® is a TLR-4 agonist and the first report of a documented role for this pharmaceutical grade immunostimulator in augmenting anti-tumor activity, suggesting that incorporation of Immunomax® into developing breast cancer therapeutic strategies may be beneficial and with less potential toxicity than checkpoint inhibitors.