Batf3 DCs and the 4-1BB/4-1BBL axis are required at the effector phase in the tumor microenvironment for PD-1/PD-L1 blockade efficacy.

The cellular source of positive signals that reinvigorate T cells within the tumor microenvironment (TME) for the therapeutic efficacy of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade has not been clearly defined. We now show that Batf3-lineage dendritic cells (DCs) are essential in this process. Flow cytometric analysis, gene-targeted mice, and blocking antibody studies revealed that 4-1BBL is a major positive co-stimulatory signal provided by these DCs within the TME that translates to CD8 T cell functional reinvigoration and tumor regression.

Recombinant Human Collagen Type III Improves Hypertrophic Scarring by Regulating the Ratio of Type I/III Collagen.

Hypertrophic scar development is a complication associated with wound healing, impacting local appearance and function. The type I/III collagen ratio affects the extent of hypertrophic scarring; a reduced ratio can ameliorate this. In this study, recombinant human collagen type III was developed.

Conditional deletion of PTEN in peripheral T cells augments TCR-mediated activation but does not abrogate CD28 dependency or prevent anergy induction.

PTEN is thought to play a critical role in T cell activation by negatively regulating the PI3K signaling pathway important for cellular activation, growth, and proliferation. To directly eliminate PTEN in postthymic T cells for studies of functional effects, we used CAR transgenic × PTEN(flox/flox) mice, which enabled gene deletion using a Cre adenovirus in vitro. These mice were also immunized to generate stable Th1 clones that could have PTEN deleted when desired.

Homeostatic proliferation plus regulatory T-cell depletion promotes potent rejection of B16 melanoma.

Purpose: To investigate the antitumor efficacy of T-cell anergy reversal through homeostatic proliferation and regulatory T-cell (Treg) depletion in a clinically relevant murine adoptive immunotherapy model.

Experimental Design: B16 melanoma cells were engineered to express the model SIYRYYGL (SIY) antigen to enable immune monitoring. Tumor-specific T cells expanded in tumor-challenged wild-type hosts but became hyporesponsive.

Amelioration of rat adjuvant-induced arthritis by Met-RANTES.

Objective: CC chemokines and their receptors play a fundamental role in trafficking and activation of leukocytes at sites of inflammation, contributing to joint damage in rheumatoid arthritis. Met-RANTES, an amino-terminal-modified methionylated form of RANTES (CCL5), antagonizes the binding of the chemokines RANTES and macrophage inflammatory protein 1alpha (MIP-1alpha; CCL3) to their receptors CCR1 and CCR5, respectively. The aim of this study was to investigate whether Met-RANTES could ameliorate adjuvant-induced arthritis (AIA) in the rat.

[The apoptosis-inducing activity of human selenoprotein P shorter isoform].

Objective: Human selenoprotein P (HSelP) is unique protein that contains 10 selenocysteines encoded by 10 inframe UGA, which typically function as stop codon. The function of HSelP remains unclear, in part due to the inability to express it by gene recombinant technique. This study is to investigate expression and purification of recombinant HSelP in prokaryotic expression system, and its activity to induce apoptosis in vitro.

Negative regulation of T-cell function by PD-1.

PD-1 is a receptor inducibly expressed on CD4+ and CD8+ T cells following activation. PD-1-deficient mice develop signs of autoimmunity, suggesting a negative regulatory role for PD-1 in dampening lymphocyte responses. The expression of one ligand for PD-1, designated PD-L1 or B7-H1, on tumor cells of a variety of histologies has suggested a potential mechanism for tumor escape from immune destruction.

[Development and characterization of a gemcitabine-resistant variant of human lung adenocarcinoma cell line A549].

Background & Objective: Gemcitabine (2',2-difluorodeo- xycytide) has antitumor activity in both experimental and clinical treatment of solid tumors. Although resistance to gemcitabine in ovarian cancer cell line and erythroleukemic cell line was described, there was no report on the lung cancer resistant variant. In order to elucidate the mechanism by which gemcitabine induce resistance in lung cancer, we have established the resistance to gemcitabine in human lung adenocarcinoma cell line A549 and described the characteristics of its resistant variant.

[Preparation and characterization of rabbit antibody against human selenoprotein P].

Aim: To prepare rabbit antibody against human selenoprotein P (HSelP) by using HSelP expressed in the prokaryotic expression system and identify its specificity.

Methods: HSelP gene fragment was expressed in E.Coli via IPTG induction and purified through DEAE and Ni-NTA columns sequentially.

[Mechanisms of the drug resistance of a 2', 2-difluorodeoxycytide (gemcitabine)-resistant variant of the human lung adenocarcinoma cell line].

Objective: To investigate the mechanisms of the drug resistance of gemcitabine resistance variant of the human lung adenocarcinoma cell line A549-Gem.

Method: Immunohistochemistry and RT-PCR were used to tested the expression of P-glycoprotein and transcription of mRNA of multidrug resistance gene and deoxycytidine kinase. Using a cDNA microarray compared the expression profiles between the resistant A549-Gem and the parent cell line A549.

[Antitumor effect of gene gun-mediated DNA vaccine pWRG-neu immunization in C57BL/6 mice].

Objective: To investigate the inhibitory effect of DNA vaccine immunization on neu-overexpressed melanoma growth in prophylactic treatment and anti-lung-metastasis experiments in C57BL/6 mice.

Methods: pcDNA-neu transfected into B16F10 with transfection reagent Fugene 6, neu-overexpressed cell clone B16F10-neu was selected with limited dilution method. The growth curve was drawn to analyse its proliferating character in vitro.

[Redox reactions of Sep15 and its relationship with tumor development].

Background & Objective: Sep15 is a selenium-containing protein identified in 1998. This protein may be involved in cancer etiology and it may have redox function. The objective of this study was to investigate the relationship between the redox function of Sep15 and tumor development.

[Research of the anti-tumor effect of human endostatin mediated by recombinant adeno-associated virus].

Background & Objective: It was reported that endostatin could inhibit tumor angiogenesis, then inhibit the growth and metastasis of tumor. However, there was few report about the treatment usage of endostatin. This study was designed to explore the effect of endostatin mediated with recombinant adeno-associated virus(rAAV) on tumor growth and metastasis.