CD49b Targeting Inhibits Tumor Growth and Boosts Anti-tumor Immunity.

The suppressive function of T-regulatory cells (Tregs) can have a detrimental effect on immune responses against tumor cells. Within the Treg cells subset, a new non-classical population has been reported, which expresses high levels of CD49b molecule and, depending on their activation status, can also express the canonical Tregs transcription factor Foxp3. In this report, we sought to characterize Tregs subsets in a murine melanoma model and disrupt the CD49b/CD29 axis by administering an anti-CD29 antibody in tumor-bearing mice. Our data shows that whereas in the draining lymph nodes, the Tr1 cells subset composes <5% of CD4+ T cells, in the tumor, they reach ∼30% of CD4+ T cells. Furthermore, Tr1 cells share the expression of suppressive molecules, such as Nrp-1, PD-1, and CD73, which are highly expressed on Tr1 cells found in tumor-infiltrating leukocytes (TILs). Regardless of the phenotypic similarities with cTreg cells, Tr1 cells display a low proliferative activity, as shown in the kinetics and the incorporation of 5-bromodeoxyuridine (BrdU) experiments. With the intent to impact on Tr1 cells, we administered anti-CD29 antibody into tumor mice, observing that the treatment effectively inhibits tumor growth. This effect is at least mediated by the enrichment of pro-inflammatory T cells, including IFN-γ+ cTreg and IFN-γ+ Tr1 cells (with reduced expression of IL-10), plus Th1 and Tc cells. In this study, we present Tr1 cell characterization in tumor-bearing animals and introduce CD29 as a target for tumor therapy, supported by a meta-analysis indicating that CD29 is present in human biopsies.

T regulatory cells-derived extracellular vesicles and their contribution to the generation of immune tolerance.

T regulatory (Treg) cells have a major role in the maintenance of immune tolerance against self and foreign antigens through the control of harmful inflammation. Treg cells exert immunosuppressive function by several mechanisms, which can be distinguished as contact dependent or independent. Recently, the secretion of extracellular vesicles (EVs) by Treg cells has been reported as a novel suppressive mechanism capable of modulating immunity in a cell-contact independent and targeted manner, which has been identified in different pathologic scenarios. EVs are cell-derived membranous structures involved in physiologic and pathologic processes through protein, lipid, and genetic material exchange, which allow intercellular communication. In this review, we revise and discuss current knowledge on Treg cells-mediated immune tolerance giving special attention to the production and release of EVs. Multiple studies support that Treg cells-derived EVs represent a refined intercellular exchange device with the capacity of modulating immune responses, thus creating a tolerogenic microenvironment in a cell-free manner. The mechanisms proposed encompass miRNAs-induced gene silencing, the action of surface proteins and the transmission of enzymes. These observations gain relevance by the fact that Treg cells are susceptible to converting into effector T cells after exposition to inflammatory environments. Yet, in contrast to their cells of origin, EVs are unlikely to be modified under inflammatory conditions, highlighting the advantage of their use. Moreover, we speculate in the possibility that Treg cells may contribute to infectious tolerance via vesicle secretion, intervening with CD4+ T cells differentiation and/or stability.

Relation between reduction mammaplasty and pulmonary functions.

The hypothesis that weight on the chest may diminish the compliance of the chest wall and affect chest wall dynamics guided this research. Few previous studies investigated the possibility of increasing chest compliance and pulmonary function after reduction mammaplasty. The meager results available were contradictory. The aim of this study was to determine the relation between reduction mammaplasty and pulmonary function. Thirty-three adult female patients who presented for reduction mammaplasty were included in the study. Paired t test showed nonsignificant change in pulmonary functions after reduction mammaplasty. Pearson method of statistical analysis revealed a significant positive correlation between the total weight of breast tissue removed and pulmonary function, and a negative correlation between the total postoperative breast volume and the pulmonary function. The study concluded that the more the breast tissue weight removed and the less the postoperative total breast volume, the better the postoperative pulmonary function.