High CD38 expression defines a mitochondrial function-adapted CD8 T cell subset with implications for lung cancer immunotherapy.

Despite identifying specific CD8 T cell subsets associated with immunotherapy resistance, the molecular pathways driving this process remain elusive. Given the potential role of CD38 in regulating CD8 T cell function, we aimed to investigate the accumulation of CD38CD8 T cells in lung cancer and explore its role in immunotherapy resistance. Phenotypic analysis of tumoral CD8 T cells from both lung cancer patients and immunotherapy-resistant preclinical models revealed that CD38-expressing CD8 T cells consist of CD38 and CD38 subsets.

CD39 identifies a specific CD8 + T cell population in lung adenocarcinoma-related metastatic pleural effusion.

Malignant pleural effusion (MPE), which is a complex microenvironment that contains numerous immune and tumour signals, is common in lung cancer. Gene alterations, such as driver gene mutations, are believed to affect the components of tumour immunity in the microenvironment (TIME) of non-small-cell lung cancer. In this study, we have shown that pleural CD39 + CD8 + T cells are selectively elevated in lung adenocarcinoma (LUAD) with wild-type epidermal growth factor receptor (EGFR) compared to those with newly diagnosed mutant EGFR (EGFR).

Combining local cryoablation with PD-L1 blockade synergistically eradicates established murine lung cancer by modulating mitochondrial in PD-1+CD8+ T cell.

Immune checkpoint blockade (ICB) has shown improvement in overall survival for lung cancer in clinical trials. However, monotherapies have limited efficacy in improving outcomes and benefit only a subset of patients. Combination therapies targeting multiple pathways can augment an immune response to improve survival further.

Imbalance of Circulating Monocyte Subsets in Subjects with Newly Emerged and Recurrent Hospital-Acquired Pneumonia.

Objective: Hospital-acquired pneumonia (HAP) is one of the most common diseases in the intensive care unit, where the development of disease is closely related with the host immune response. Monocytes play an important role in both innate and adaptive immune system. We aimed to investigate the changes of circulating monocyte subsets in subjects with HAP to explore its value in monitoring HAP.

4-1BB Agonism Combined With PD-L1 Blockade Increases the Number of Tissue-Resident CD8+ T Cells and Facilitates Tumor Abrogation.

Although the milestone discovery of immune checkpoint blockade (ICB) has been translated into clinical practice, only a fraction of patients can benefit from it with durable responses and subsequent long-term survival. Here, we tested the anti-tumor effect of combining PD-L1 blockade with 4-1BB costimulation in 3LL and 4T1.2 murine tumor models.

Investigating the role of circulating CXCR5-expressing CD8+ T-cells as a biomarker for bacterial infection in subjects with pneumonia.

Background: Recently, lymphoid follicle-confined and circulating CD8+ T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5) were described, which was involved in anti-virus immune response. However, the dynamics and role of circulating CXCR5-expressing CD8+ T-cells during bacterial infection is unknown. So, we asked whether CXCR5+ CD8+ T cells were also generated during bacterial infections in lower respiratory tract.

Membranous and Cytoplasmic Expression of PD-L1 in Ovarian Cancer Cells.

Background: Expression of programmed death-ligand 1 (PD-L1) on tumor cells represents a powerful immune evasion pathway, but the role of intracellular or cytoplasmic PD-L1 has not been investigated in ovarian cancer cells.

Methods: Flow cytometry (FCM), Real-time PCR (qPCR), immunohistochemistry (IHC) and western blot were used to determine the expression of PD-L1 in ovarian cancer cells. The cytokines detected in the tumor or tumor associated macrophage (TAM) were used to treat cancer cells.

Analysis of B7-H4 expression in metastatic pleural adenocarcinoma and therapeutic potential of its antagonists.

Background: The increasing incidence and poor outcome associated with malignant pleural effusion (MPE) requires finding an effective treatment for this disease. Inhibitory B7-H4 is expressed in many different human cancers but its role in malignant pleural tissue has yet to be established.

Methods: Here, patients with metastatic pleural adenocarcinoma (MPA) or with early-stage lung adenocarcinoma were clinically and statistically analyzed.

The increase of circulating PD-L1-expressing CD68(+) macrophage in ovarian cancer.

Tumor-associated macrophages (TAMs) have been characterized as a critical population of immunosuppressive cells in a variety of tumor types. PD-L1 (also termed B7-H1) has been described to exert co-inhibitory and immune regulatory functions. Here, in ovarian cancer, PD-L1 is selectively overexpressed on some TAM compared that of benign ovarian disease.

Soluble CD40 in plasma and malignant pleural effusion with non-small cell lung cancer: A potential marker of prognosis.

Objective: Soluble CD40 (sCD40) is a potential modulator for both antitumor responses and CD40-based immunotherapy; however the levels and significance of sCD40 in non-small cell lung cancer (NSCLC) patients with malignant pleural effusion are unknown.

Methods: Forty-eight patients with lung cancer were treated in our institutions from January 2008 to January 2010. Peripheral blood and pleural effusion samples were collected from each subject.

[Preliminary study of breast cancer magnetic resonance targeting diagnosis basing on magnetic nanoparticles in vitro].

Objective: To develop a magnetic nanoparticles based magnetic resonance (MR) probe targeting CD40 mutant in the imaging of breast cancer cells in vitro.

Methods: For preparing an immunologically competent probe, monoclonal antibody was conjugated with ultrasmall superparamagnetic iron oxide (USPIO) particles basing on chemical cross-linking method.Its bioactivity was analyzed with flow cytometry, confocal microscopy and Prussian blue staining.

CD40 signal regulates CXCR4 mediating ovarian carcinoma cell migration: implications for extrapelvic metastastic factors.

Ovarian carcinomas are highly invasive, especially in the peritoneal cavity. SDF-1α and its receptor, CXCR4, play a crucial role in migration of cancer cells. Here, SDF-1α directed HO8910 cell migration, but not SKOV3 cells.

Induced expression of B7-H3 on the lung cancer cells and macrophages suppresses T-cell mediating anti-tumor immune response.

Macrophages are the prominent components of solid tumors and have complex dual functions in their interaction with cancer cells. Strong evidence suggests that TAM is a part of inflammatory circuits that promote tumor progression. B7-homologue 3 (B7-H3), a recently identified homologue of B7.

[Construction of eukaryotic expression vector of muCD40-IgG1Fc fusion protein and its expression in CHO cells].

Aim: To construct an eukaryotic expression vector of human muCD40Ig fusion protein, and to express it stably in Chinese hamster ovary (CHO) cells for obtaining muCD40Ig fusion protein and founding an experimental basis for investigating the soluble muCD40 molecule in vivo.

Methods: Extracellular domain of human muCD40 gene was amplified by RT-PCR from L929/muCD40-transfected cells, and the genes encoding the constant regions of human IgG1 were cloned from human splenocytes. The genes were inserted into eukaryotic expression vector pIRES2-EGFP, respectively.

Analysis of CD8+CD28- T-suppressor cells in gastric cancer patients.

Host anti-tumor immune responses can be attenuated by suppressor T cells of the phenotype CD8(+)CD28(-) (T(s) cells). In the present study, we investigated the presence of CD8(+)CD28(-) (T(s) cells) in the peripheral blood compartment of gastric cancer (GC) patients. Flow cytometry was used to detect the population of CD8(+)CD28(-) T(s) cells present in peripheral blood in therapy naïve patients with gastric cancer (n = 26), postoperative chemotherapy naïve gastric cancer patients (n = 23), and healthy controls (n = 27).

Induced expression of B7-H4 on the surface of lung cancer cell by the tumor-associated macrophages: a potential mechanism of immune escape.

B7-homolog 4 (B7-H4), a recently identified homolog of B7.1/2 (CD80/86), has been described to exert co-stimulatory and immune regulatory functions. We investigated the expression and the functional activity of B7-H4 in lung cancer in vitro and in vivo.

Overexpression of B7-H4 in tumor infiltrated dendritic cells.

DCs infiltrated tumors appears to be phenotypically and functionally defective. B7-H4 was highlighted for its inhibitory role in T cell responses. In this study, we showed that B7-H4 was moderately expressed in imDCs, and up-regulated by IL-10, and TNF-α could counteract the up-regulatory effects of IL-10 on expression of B7-H4 in DCs in vitro.

CD40 is overexpressed by HPV16/18-E6 positive cervical carcinoma and correlated with clinical parameters and vascular density.

CD40 is expressed in many tumor cells, however, its role in tumor biology is yet to be demonstrated. In the present study, we investigated the role of CD40 in cervical carcinoma. In vivo, we evaluated CD40 expression in 56 cervical carcinoma tissues, 43 cervicitis and 38 normal cervix, and investigated the relationship between CD40 and HPV antigen, histopathological parameters, vascular density, and vascular endothelial growth factor (VEGF) expressions.

Sensitization of SiHa cell to gemcitabine by CD40 activation and its overexpression in cervical carcinoma.

CD40, a member of the tumor necrosis factor receptor superfamily, is widely expressed on various cell types. Some studies show that CD40 expression is related to several carcinomas, where its function remains largely unknown. This study investigated the expression of CD40 on cervical carcinoma and evaluated the effect of agnostic anti-CD40 mAb (5C11) on tumor cell line (SiHa).

Preparation and characterization of a novel chimeric antibody against human CD40 with the potential to inhibit Daudi cell proliferation.

5C11, a murine monoclonal antibody with a high specificity for human CD40 molecule, is a promising candidate for cancer targeting therapy. We have therefore attempted to construct a humanized antibody of 5C11 to minimize its immunogenicity for potential clinical use. A chimeric version of 5C11 (ch-5C11) was generated by transferring these mouse variable regions onto a human framework.

CD40-activated apoptotic tumor cell-pulsed dendritic cell could potentially elicit antitumor immune response: involvement of up-regulation of B7-H3 expression.

Dendritic cells (DCs) initiate and direct immune responses. Previous in vitro and in vivo studies have showed that DCs matured with CD40 linking signal could potentially elicit and boost antitumor immunity, however, its molecular mechanism remain elusive. This study demonstrates that expression of B7-H3 on apoptotic cell-loading DCs is up-regulated markedly by CD40 activation but not by tumor necrosis factor-alpha stimulation.

[Expression of human-mouse chimeric antibody against CD40 in CHO cell line and characterization of its function].

Aim: To investigate the stable expression of a chimeric antibody against CD40 moleculeèch-5C11éin CHO and its biological activity.

Methods: Human-mouse chimeric antibody against CD40 recombinant plasmid and mock plasmid were transfected into CHO cell line through lipofectamine mediation. Human kappa chain and Fc fragment of ch-5C11 were characterized by FACS and Western blot.

Expression of programmed-death receptor ligands 1 and 2 may contribute to the poor stimulatory potential of murine immature dendritic cells.

Recent data have revealed that Ag presentation by immature dendritic cells (imDCs) plays a role in establishing and maintaining T-cell tolerance, but the mechanism remains unclear. PD-L1 and PD-L2, ligands for programmed-death receptor 1 (PD-1), members of the expanding B7 family, were highlighted for their inhibitory role in T-cell responses. Here, we show that blockade of PD-1 ligands on imDCs resulted in enhanced T-cell proliferation, which is perhaps due to the enhancement of IL-2 production from DC-stimulated T cells.

[Construction and expression of human-mouse chimeric antibody against human CD40].

Aim: To construct and express a chimeric antibody against human CD40 molecule by genetic engineering antibody transformation.

Methods: Total RNA was extracted from the murine hybridoma cell 5C11 which secreted anti-CD40 monoclonal antibody (mAb). The genes encoding V(H) and V(L) of mAb 5C11 were amplified by RT-PCR.