Simultaneous inhibition of EGFR/VEGFR and cyclooxygenase-2 targets stemness-related pathways in colorectal cancer cells.

Despite the demonstrated benefits of anti-EGFR/VEGF targeted therapies in metastatic colorectal cancer (mCRC), many patients initially respond, but then show evidence of disease progression. New therapeutic strategies are needed to make the action of available drugs more efficient. Our study aimed to explore whether simultaneous targeting of EGFR/VEGF and cyclooxygenase-2 (COX-2) may aid the treatment and management of mCRC patients.

Klotho modulates the stress response in human senescent endothelial cells.

Lack of Klotho expression in mice leads to premature aging and age-related diseases, including vascular diseases. The aim of this study was to determine how endothelial cell line senescence affects Klotho expression and whether intra- or extracellular Klotho has any effect on the response of senescent cells to oxidative stress. The study was performed using human endothelial cells (HUVEC); cell aging was obtained by prolongation of cell division to 42 population doublings (PD).

Exploring the pan-surfome of Streptococcus suis: looking for common protein antigens.

Streptococcus suis is a swine and human pathogen for which no commercial vaccine is still available. Conserved and broadly distributed surface proteins have become the chosen targets for the development of efficacious vaccines that could overcome the problems of non-heterologous protection of bacterins or capsule polysaccharide-based vaccines. In this work, we have analyzed by proteomics a collection of 39 strains obtained from infected pigs.

Correlation of effector function with phenotype and cell division after in vitro differentiation of naive MART-1-specific CD8+ T cells.

Adoptive transfer of antigen-specific CD8+ T cells may represent an effective strategy for immunotherapy of tumors such as melanoma, but is limited by the number and functionality of in vitro expanded T cells. Here, we document that although ELAGIGILTV-specific CD8+ T cells from different donors initially possessed a naive phenotype, after antigen-induced in vitro expansion two distinct phenotypes correlating with cell proliferation rate emerged in the different donors. Those cultures achieving fewer cumulative population doublings (CPDs) were cytotoxic and displayed a CD45RA+CCR7- phenotype.

Invariant NKT and NKT-like lymphocytes: two different T cell subsets that are differentially affected by ageing.

The expression on T lymphocytes of surface receptors that are characteristically expressed on NK cells has led to the definition of a T cell subset that has been termed Natural Killer T (NKT) cells. Thus NKT cells constitute a minor lymphocyte population that exhibits features of both T cells and NK cells. However, the term 'NKT cell' has been applied variably to cells that express a restricted T-cell receptor (TCR) that recognizes glycolipids (alpha-GalCer) presented by the MHC-like molecule CD1d and that express CD161, as well as populations of conventional CD8 T cells that show up-regulated expression of NK-cell markers.

Immunological biomarkers of ageing in man: changes in both innate and adaptive immunity are associated with health and longevity.

Scientific and clinical advances in the last century have led to increased numbers of individuals living to older ages. Thus a major concern is how to live these years with a high quality of life. The ageing immune system is less well able to cope with infectious diseases than the youthful immune system probably as a consequence of altered immune response to pathogens.

Decreased frequency and proliferative response of invariant Valpha24Vbeta11 natural killer T (iNKT) cells in healthy elderly.

Invariant natural killer T (iNKT) cells represent a well-established T cell lineage characterised in humans by TCR consisting of an invariant alpha chain encoded by Valpha24-JalphaQ genes, paired preferentially with a Vbeta11 chain. iNKT cells also share some characteristics with NK cells, such as the expression of the NK-associated receptor CD161 in humans. The T cell immune response is the most dramatically affected by ageing, although age-associated alterations in the phenotype and function of other cells of the immune system have been demonstrated.

CD8 T cells expressing NK associated receptors are increased in melanoma patients and display an effector phenotype.

CD8+ T cells can express NK-associated receptors (NKRs) that may regulate their cytolytic function. We have characterized the expression of several NKRs on peripheral blood CD8+ T cells from melanoma patients and compared them to age-matched healthy donors. The analysis performed includes HLA class I specific receptors (KIRs, LILRB1 and CD94/NKG2) and other NK receptors like CD57, CD56 and CD16.

Expression of NK-associated receptors on cytotoxic T cells from melanoma patients: a two-edged sword?

The coexistence of tumor progression with a tumor-specific immune response constitutes a major paradox of tumor immunity. During the last decade, the presence of cytotoxic T lymphocytes (CTLs) recognising melanoma-associated antigens has been unequivocally demonstrated in numerous different in vivo and in vitro models. However, most often these melanoma-specific T lymphocytes do not control tumor growth.