Despite major advances with immunotherapy and targeted therapy in the past decade, metastatic melanoma continues to be a deadly disease for close half of all patients. Over advancement immune profiling deeper understanding tumor microenvironment (TME) have enabled development novel approaches targeting multitude targets being investigated melanoma. However, date, checkpoint blockade has remaine...

Regulatory T cells (Treg) comprise multiple subsets and are important in controlling immunity and inflammation. However, the induction and mode of action of the various distinct Treg subsets remain ill defined, particularly in humans. Here, we describe a human CD8+ lymphocyte activation gene-3 (LAG-3)+CD25+FoxP3+ Treg subset, which suppresses T cells partly through the secretion of CC chemokine...

Data have been reported on the in vivo adjuvant role of soluble lymphocyte activation gene-3 (LAG-3) recombinant protein in mouse models and on its ability to support the in vitro generation of human, tumor-specific CTLs. In this study, we show that soluble human rLAG-3 protein (hLAG-3Ig) used in vitro as a single maturation agent induces phenotypic maturation of monocyte-derived dendritic cell...

Immune checkpoint inhibition has been shown to successfully reactivate endogenous T cell responses directed against tumor-associated antigens, resulting in significantly prolonged overall survival in patients with various tumor entities. For malignancies with low endogenous immune responses, this approach has not shown a clear clinical benefit so far. Therapeutic vaccination, particularly dendr...

Therapeutic cancer vaccines are designed to treat cancer by boosting the endogenous immune system to fight against the cancer. In the development of clinically effective cancer vaccines, one of the most practical objectives is to identify adjuvants that are capable of optimizing the vaccine effects. In this study, we explored the potential of polyinosinic-polycytidylic acid (poly(I:C)) and LAG-...

Tight control of T-cell proliferation and effector function is essential to ensure an effective but appropriate immune response. Here, we reveal that this is controlled by the metalloprotease-mediated cleavage of LAG-3, a negative regulatory protein expressed by all activated T cells. We show that LAG-3 cleavage is mediated by two transmembrane metalloproteases, ADAM10 and ADAM17, with the acti...

Concurrent blockade of LAG-3 may enhance efficacy anti-programmed cell death-1 (PD-1) therapies. We present updated safety and clinical activity data from patients (pts) with advanced mel treated concurrent anti-LAG-3 (fianlimab) anti-PD-1 (cemiplimab). This Phase 1 study included pts unresectable or metastatic (excluding uveal mel) who were anti–PD-ligand (L)1 treatment naïve (expansion cohort...

Immuno-oncology (IO) therapies, used alone or in combination, have improved outcomes advanced hepatocellular carcinoma (HCC); however, not all patients benefit and novel IO combinations are needed to further enhance the benefit-risk profile. Lymphocyte-activation gene 3 (LAG-3) regulates an inhibitory immune checkpoint pathway, limiting T-cell activity, is a marker for exhaustion resistance the...

Yeast cells that inherit mutations at the PEP4 locus exhibit a pronounced phenotypic lag in the expression of the mutant phenotype imparted by these mutations. This lag appears to extend to all of the enzymes that are affected by the pep4-3 mutation. For at least two of the enzymatic activities, phenotypic lag shows mitotic cosegregation. Phenotypic lag is found for meiotic progeny and for mito...