2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer

Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer

The Role of Mechanism of Action of CD200:CD200R1 Interaction in Breast Cancer

Cancer cells can use immune inhibitory receptors to evade the host’s anti-tumour responses and establish immunosuppressive networks in the tumour microenvironment. In this thesis, we investigated the interaction between the immunosuppressive molecule CD200 with its receptor, CD200R1, in breast cancer. We found that CD200 is expressed in the local tumour microenvironment in human breast cancer patients and developed a mouse model to study the effect of CD200 on tumour growth and metastasis. Using mouse-derived EMT6 breast cancer cells and BALB/c female hosts, we explored the effects of overexpressing and silencing the expression of CD200 and CD200R1 in hosts and tumour cells. CD200 expression by host and tumour cells enhanced tumour growth and metastasis to draining lymph nodes (DLN). Silencing CD200 expression in EMT6 tumour cells led to a reduction in primary tumour size and metastasis, as well as an increase in anti-tumour cytotoxic responses in the host. Lack of CD200R1 expression in the host resulted in a marked decrease in breast cancer development and CD200R1-/- mice were able to mount specific anti-EMT6 immune response that could be adoptively transferred to wild type naïve hosts. In addition, we extended our findings to a model in which anti-tumour immunity was explored in EMT6 tumour-bearing hosts lacking CD200 expression and treated with a combination of immunotherapy with the non-conventional chemotherapeutic agent, metformin. The findings suggest that CD200 may be an important prognostic marker and a target for breast cancer treatment that could synergize with other therapies and improve outcomes in patients.Ph.D

Sex & the Immune Response: Why Taking Sex into Account is Essential to New Immunoregulatory Approaches for Treating Breast Cancer

The immune system plays an important role in the development of cancer, and immune cells have recently become targets for treatments. The immune systems of males and females have important sex-based differences that depend, in part, on differential responses of immune cells to steroid hormones, such as estrogens, progesterone, and androgens. This essay, drawing from insights and advocacy from social scientists, argues that therapeutic interventions and research with animal models should take sex into account because there are many sex-based differences that affect immunocompetence8, susceptibility to infection, and severity of illness. The development of therapies that target the immune cells in cancer patients should be sex/gender inclusive, considering differential immune responses in men and women

Comparison of Immunity in Mice Cured of Primary/Metastatic Growth of EMT6 or 4THM Breast Cancer by Chemotherapy or Immunotherapy

<div><p>Purpose</p><p>We have compared cure from local/metastatic tumor growth in BALB/c mice receiving EMT6 or the poorly immunogenic, highly metastatic 4THM, breast cancer cells following manipulation of immunosuppressive CD200:CD200R interactions or conventional chemotherapy.</p><p>Methods</p><p>We reported previously that EMT6 tumors are cured in CD200R1KO mice following surgical resection and immunization with irradiated EMT6 cells and CpG oligodeoxynucleotide (CpG), while wild-type (WT) animals developed pulmonary and liver metastases within 30 days of surgery. We report growth and metastasis of both EMT6 and a highly metastatic 4THM tumor in WT mice receiving iv infusions of Fab anti-CD200R1 along with CpG/tumor cell immunization. Metastasis was followed both macroscopically (lung/liver nodules) and microscopically by cloning tumor cells at limiting dilution in vitro from draining lymph nodes (DLN) harvested at surgery. We compared these results with local/metastatic tumor growth in mice receiving 4 courses of combination treatment with anti-VEGF and paclitaxel.</p><p>Results</p><p>In WT mice receiving Fab anti-CD200R, no tumor cells are detectable following immunotherapy, and CD4+ cells produced increased TNFα/IL-2/IFNγ on stimulation with EMT6 in vitro. No long-term cure was seen following surgery/immunotherapy of 4THM, with both microscopic (tumors in DLN at limiting dilution) and macroscopic metastases present within 14 d of surgery. Chemotherapy attenuated growth/metastases in 4THM tumor-bearers and produced a decline in lung/liver metastases, with no detectable DLN metastases in EMT6 tumor-bearing mice-these latter mice nevertheless showed no significantly increased cytokine production after restimulation with EMT6 in vitro. EMT6 mice receiving immunotherapy were resistant to subsequent re-challenge with EMT6 tumor cells, but not those receiving curative chemotherapy. Anti-CD4 treatment caused tumor recurrence after immunotherapy, but produced no apparent effect in either EMT6 or 4THM tumor bearers after chemotherapy treatment.</p><p>Conclusion</p><p>Immunotherapy, but not chemotherapy, enhances CD4⁺ immunity and affords long-term control of breast cancer growth and resistance to new tumor foci.</p></div

Specific protection from re-challenge with EMT6, but not 4THM, assaying either local tumor growth (panel a) or DLN metastases (panel c) in mice treated 90 d earlier by surgical tumor resection and immunotherapy.

<p>Naïve mice had had no previous EMT6 or 4THM tumor implants. All mice were sacrificed at 20 d post re-challenge. Data represent mean<u>s</u> for group. No protection was seen in mice initially treated with 4THM tumors before treatment/re-challenge (panel b). *, p<0.05 compared with equivalent fresh control mice.</p

Comparison of lung and liver metastases of tumor cells in WT BALB/c mice receiving EMT6 or 4THM tumor cells and subsequently treated with surgical resection and chemotherapy/immunotherapy (see )Methods.

<p>4 mice were used per group, with mice sacrificed at the times show post surgery (number above histogram bars) to measure macroscopic tumor metastases in the lung/liver. All data represent arithmetic means (±SD) for each group. nc indicates no metastatic colonies detected; *, p<0.05 relative to similar group receiving either immunotherapy or chemotherapy.</p

Attenuation of outgrowth of tumor from DLN of mice shown in <b>Figure 1</b> as assessed by limiting dilution frequency (see Methods).

<p>DLN cells from separate mice were also cloned alone at the time of surgery (data to far left of each panel-control*). All frequencies were calculated based on the input numbers of cells from DLN of control mice only. *, p<0.05 compared with control* mice</p