Case-Control Study of Fetal Microchimerism and Breast Cancer

Prior pregnancy is known to protect against development of breast cancer. Recent studies have demonstrated that pregnancy has the capacity to establish small numbers of immunologically active fetal-derived cells in the mother, a phenomenon known as fetal microchimerism (FMc). We asked whether presence of FMc, routinely acquired during pregnancy, is a protective factor for breast cancer.DNA extracts from peripheral blood specimens were obtained from a population-based case-control study of risk factors for breast cancer in women 21 to 45 years old. Specimens were tested with quantitative PCR for presence and concentrations of male DNA presumed to derive from prior pregnancies with a male fetus. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with consideration of multiple established reproductive and environmental risk factors for breast cancer. FMc results were generated on 99 parous women, 54 with primary invasive breast cancer and 45 general population controls. FMc prevalence was 56% (25/45) and 26% (14/54) in controls and cases, respectively. Women harboring FMc were less likely to have had breast cancer (OR = 0.29, 95% CI 0.11-0.83; p = 0.02, adjusting for age, number of children, birth of a son, history of miscarriage, and total DNA tested). In addition, FMc concentrations were higher in controls versus cases (p = 0.01). Median concentrations were 2 (0-78) and 0 (0-374) fetal genomes/10(6) maternal genomes in controls and cases, respectively.Results suggest that the enigma of why some parous women are not afforded protection from breast cancer by pregnancy might in part be explained by differences in FMc. Mechanistic studies of FMc-derived protection against breast cancer are warranted

Non-conventional sources of peptides presented by MHC class I

Effectiveness of immune surveillance of intracellular viruses and bacteria depends upon a functioning antigen presentation pathway that allows infected cells to reveal the presence of an intracellular pathogen. The antigen presentation pathway uses virtually all endogenous polypeptides as a source to produce antigenic peptides that are eventually chaperoned to the cell surface by MHC class I molecules. Intriguingly, MHC I molecules present peptides encoded not only in the primary open reading frames but also those encoded in alternate reading frames. Here, we review recent studies on the generation of cryptic pMHC I. We focus on the immunological significance of cryptic pMHC I, and the novel translational mechanisms that allow production of these antigenic peptides from unconventional sources

Chimerism and outcomes after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning

Allogeneic hematopoietic cell transplantation ( HCT) following nonmyeloablative conditioning has been extensively evaluated in patients with hematologic malignancies who are ineligible for conventional HCT because of age or medical comorbidities. Nonmyeloablative regimens have led to an initial state of mixed hematopoietic chimerism defined as coexistence of donor- and host-derived hematopoiesis. While nonmyeloablative regimens have been associated with reduced regimen-related toxicities in comparison with conventional myeloablative conditioning, graft rejection, graft-versus-host disease ( GVHD), and disease progression have remained significant challenges. In this article, after briefly introducing current techniques for chimerism assessment, we describe factors affecting donor chimerism levels after nonmyeloablative conditioning, and then review data suggesting that chimerism assessment early after HCT might help identify patients at risk for graft rejection, GVHD and relapse/progression. Finally, we discuss how these observations have opened the way to further research protocols evaluating manipulation of postgrafting immunosuppression, and/or infusion of donor immune cells