Maternal obesity increases offspring's mammary cancer recurrence and impairs tumor immune response.

Over 50% of women at a childbearing age in the United States are overweight or obese, and this can adversely affect their offspring. We studied if maternal obesity-inducing high fat diet (HFD) not only increases offspring's mammary cancer risk but also impairs response to antiestrogen tamoxifen. Female rat offspring of HFD and control diet-fed dams, in which estrogen receptor-positive (ER+) mammary tumors were induced with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA), exhibited similar initial responses to antiestrogen tamoxifen. However, after tamoxifen therapy was completed, almost all (91%) tumors recurred in HFD offspring, compared with only 29% in control offspring. The increase in local mammary tumor recurrence in HFD offspring was linked to an increase in the markers of immunosuppression (Il17f, Tgfß1, VEGFR2) in the tumor microenvironment (TME). Protein and mRNA levels of the major histocompatibility complex II (MHC-II), but not MHC-I, were reduced in the recurring DMBA tumors of HFD offspring. Further, infiltration of CD8+ effector T cells and granzyme B+ (GZMB+) cells were lower in their recurring tumors. To determine if maternal HFD can pre-program similar changes in the TME of allografted E0771 mammary tumors in offspring of syngeneic mice, flow cytometry analysis was performed. E0771 mammary tumor growth was significantly accelerated in the HFD offspring, and a reduction in the numbers of GZMB and non-significant reduction of interferon γ (IFNγ) secreting CD8+ T cells in the TME was seen. Thus, consumption of a HFD during pregnancy increases susceptibility of the female rat and mouse offspring to tumor immune suppression and mammary tumor growth and recurrence.

PD-1 deficiency augments bone marrow failure in a minor-histocompatibility antigen mismatch lymphocyte infusion model.

Although PD-1 blockade has revolutionized cancer immunotherapy, immune-related adverse events (irAEs) present life-threatening complications. Recent reports of aplastic anemia (AA) as irAEs implicate PD-1/PD-L1 as important in preventing immune-mediated destruction of the hematopoietic niche. Infusion of PD-1-deficient (PD-1 knockout [KO]) lymph node (LN) cells into minor-antigen mismatched mice resulted in early mortality, as well as more severe bone marrow (BM) hypoplasia, anemia, and BM microarchitecture disruption in PD-1 KO LN-infused mice relative to mice that received B6 LN cell infusion. Mice that received PD-1 KO LN cells had more CD8+ T-cell infiltration of the BM and greater expansion of H60-specific CD8+ T cells than did their B6 LN-infused counterparts. In the spleen, CD8+ T cells were skewed to an effector memory phenotype, suggesting accelerated differentiation of PD-1 KO T cells. Our data suggest that PD-1 dysregulation has a role in murine BM failure and vigilance in irAE monitoring may be desirable to treat early AA and related cytopenias.

Roles of cancer/testis antigens (CTAs) in breast cancer.

Breast cancer is the most common cancer diagnosed and is the second leading cause of cancer death among women in the US. For breast cancer, early diagnosis and efficient therapy remains a significant clinical challenge. Therefore, it is necessary to identify novel tumor associated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens (CTAs) have emerged as a potential clinical biomarker targeting immunotherapy for various malignancies due to the nature of its characteristics. CTAs are a group of tumor associated antigens (TAAs) that display normal expression in immune-privileged organs, but display aberrant expression in several types of cancers, particularly in advanced cancers. Investigation of CTAs for the clinical management of breast malignancies indicates that these TAAs have potential roles as novel biomarkers, with increased specificity and sensitivity compared to those currently used in the clinic. Moreover, TAAs could be therapeutic targets for cancer immunotherapy. This review is an attempt to address the promising CTAs in breast cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions.

Effect of steady magnetic field on laser-induced breakdown spectroscopy.

Effects of a steady magnetic field on the laser-induced breakdown spectroscopy of certain elements (Mn, Mg, Cr, and Ti) in aqueous solution were studied, in which the plasma plume expanded across an external steady magnetic field (approximately 6 kilogauss). Nearly 1.6 times enhancement in the line emission intensity was observed in the presence of the magnetic field. The temporal evolution of the line emission showed a significant enhancement in plasma emission between 2- and 7- micro(s) gate delays for Mg in the presence of the magnetic field (5-30 micro(s) for Mn). This enhancement in the emission is attributed to an increase in the rate of recombination because of an increase in plasma density due to a magnetic confinement after cooling the plasma. The increase in the optical line emission due to magnetic confinement was absent when the plasma was hot with a dominant background (continuum) emission. The limits of detection of Mg and Mn were reduced by a factor of two in the presence of a steady magnetic field of 5 kilogauss.

Evaluation of the potential of laser-induced breakdown spectroscopy for detection of trace element in liquid.

The analytical figure of merit of the potential of laser-induced breakdown spectroscopy (LIBS) has been evaluated for detection of trace element in liquid. LIBS data of Mg, Cr, Mn, and Re were studied. Various optical geometries, which produce the laser spark in and at the liquid sample, were tested. The calibration curves for Mg, Cr, Mn, and Re were obtained at the optimized experimental conditions with bulk liquid and in liquid jet. It was found that measurements using a liquid jet provide better detection limits than bulk liquid measurements. The limits of detection (LOD) of Mg, Cr, Mn, and Re in the present liquid jet measurement are found to be 0.1, 0.4, 0.7, and 8 ppm, respectively. The LOD of Mg using Mg 279.55 nm was compared with the values found in other liquid work.