With the in-depth study of tumor immunity, immunotherapy represented by immune checkpoint inhibitors has made a great breakthrough in solid tumors. Small cell lung cancer (SCLC) accounts for about 15%-20% of all lung cancers, with high malignancy, early metastasis and lack of effective treatment strategy. The appearance of immune checkpoint inhibitors brings new hope for SCLC. Several clinical trials have demonstrated the persistent efficacy and clinical activity of the programmed death receptor/ligand 1 (PD-1/L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) in the treatment of SCLC. However, its efficacy and safety are not very accurate, and the markers that can effectively predict the efficacy of immunotherapy have not been concluded. In this paper, for further changing the treatment strategy of SCLC clinical practice and providing theoretical basis of research, we reviewed the progress of immune checkpoint inhibitors, related markers in the treatment of SCLC by exploring the value, problems and challenges of immunotherapy in SCLC.
.
Humans ; Lung Neoplasms ; diagnosis ; drug therapy ; immunology ; Molecular Targeted Therapy ; methods ; Prognosis ; Small Cell Lung Carcinoma ; diagnosis ; drug therapy ; immunology

OBJECTIVEProspective research demonstrated that Chinese regimen granules of Shenyang could prolong survival time and improve survival rate of patients with oral squamous cell carcinoma (SCC). But the mechanism was not clear. The purpose of this study was to investigate Shenyang's effect on peripheral blood lymphocyte subsets of SD rats with SCC of tongue and explore immunological mechanism.

METHODSAmong 80 SD rats fed by 0.002% 4-nitroquinoline-1-oxide (4NQO) drinking water for 36 weeks, 61 rats with SCC of tongue had been found and were randomly divided into 4 groups, namely Shenyang A, Shenyang B, positive and blank control groups. Before and after high and normal dosage of Shenyang, acanthopanax senticoside and water had been given for 15 days respectively, peripheral blood lymphocyte subsets were detected with flow cytometry. The data were statistically analyzed with paired t Test.

RESULTSPercentage of CD3+ CD4+ T cell and CD3-CD161a+ NK cell, ratio of CD4+/CD8+ were increased. Percentage of CD3+CD8+ T cell was decreased, and the effect was better than that of acanthopanax senticoside in improving the percentage of CD3-CD161a+ NK cell.

CONCLUSIONAmong anti-tumor mechanisms of Shenyang it is that corrects disorder of lymphocyte subsets and increases percentage of CD3-CD161a+ NK cell.

Animals ; Carcinoma, Squamous Cell ; drug therapy ; immunology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Lymphocyte Subsets ; drug effects ; immunology ; Rats ; Rats, Sprague-Dawley ; Tongue Neoplasms ; drug therapy ; immunology

Adenocarcinoma ; drug therapy ; immunology ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; drug therapy ; immunology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Killer Cells, Natural ; immunology ; Lung Neoplasms ; drug therapy ; immunology ; Male ; Middle Aged ; Phytotherapy ; Quality of Life ; T-Lymphocyte Subsets ; immunology

Antineoplastic Agents ; chemistry ; pharmacology ; Carcinoma, Hepatocellular ; drug therapy ; immunology ; pathology ; Cytokines ; immunology ; Drug Screening Assays, Antitumor ; Glypicans ; antagonists & inhibitors ; immunology ; Humans ; Ligands ; Liver Neoplasms ; drug therapy ; immunology ; pathology ; T-Lymphocytes ; drug effects ; immunology

Antibody-based PD-1/PD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre-existing T-cell function to modulate antitumor immunity. In this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-1/PD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural information will benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.
Antibodies, Monoclonal ; immunology ; therapeutic use ; Antibodies, Monoclonal, Humanized ; immunology ; therapeutic use ; B7-H1 Antigen ; antagonists & inhibitors ; immunology ; Humans ; Neoplasms ; drug therapy ; immunology ; pathology ; Programmed Cell Death 1 Receptor ; antagonists & inhibitors ; immunology ; Signal Transduction ; drug effects ; immunology ; T-Lymphocytes ; immunology

Evidence has indicated that low doses of anti-tumor regimens can induce cell apoptosis in vitro, although different regimens induce apoptosis by different mechanism and pathway. In recent years, new tumor treatment strategy has been mainly focused on inducing tumor cell apoptosis. The present review discusses the advantages and disadvantages of inducing tumor cell apoptosis. The benefit of inducing apoptosis is not to cause inflammatory reaction, but as its disadvantage, it inhibits immune responses, and the phagocytosis of apopotic bodies may result in horizontal transfer of genes (including oncogenes and other oncogenic materials), which can be one of the causes of tumor relapse. This paper proposes that the tumor treatment strategy should be turn into promoting tumor cell necrosis and inducing anti-tumor immune responses.
Antineoplastic Agents ; therapeutic use ; Apoptosis ; drug effects ; Humans ; Necrosis ; chemically induced ; Neoplasms ; drug therapy ; immunology ; pathology

Antineoplastic Agents, Immunological ; immunology ; pharmacology ; Cell Line, Tumor ; GPI-Linked Proteins ; antagonists & inhibitors ; immunology ; Humans ; Neoplasm Proteins ; analysis ; immunology ; Pancreatic Neoplasms ; drug therapy ; immunology ; pathology

Transforming growth factor (TGF)-β regulates a wide variety of cellular responses, including cell growth arrest, apoptosis, cell differentiation, motility, invasion, extracellular matrix production, tissue fibrosis, angiogenesis, and immune function. Although tumor-suppressive roles of TGF-β have been extensively studied and well-characterized in many cancers, especially at early stages, accumulating evidence has revealed the critical roles of TGF-β as a pro-tumorigenic factor in various types of cancer. This review will focus on recent findings regarding epithelial-mesenchymal transition (EMT) induced by TGF-β, in relation to crosstalk with some other signaling pathways, and the roles of TGF-β in lung and pancreatic cancers, in which TGF-β has been shown to be involved in cancer progression. Recent findings also strongly suggested that targeting TGF-β signaling using specific inhibitors may be useful for the treatment of some cancers. TGF-β plays a pivotal role in the differentiation and function of regulatory T cells (Tregs). TGF-β is produced as latent high molecular weight complexes, and the latent TGF-β complex expressed on the surface of Tregs contains glycoprotein A repetitions predominant (GARP, also known as leucine-rich repeat containing 32 or LRRC32). Inhibition of the TGF-β activities through regulation of the latent TGF-β complex activation will be discussed.
Drug Discovery ; Humans ; Lung Neoplasms ; drug therapy ; immunology ; metabolism ; Membrane Proteins ; metabolism ; Pancreatic Neoplasms ; drug therapy ; immunology ; metabolism ; Signal Transduction ; drug effects ; physiology ; T-Lymphocytes, Regulatory ; metabolism ; Transforming Growth Factor beta ; antagonists & inhibitors ; immunology ; metabolism

OBJECTIVETo observe the therapeutic effects of beta-elemene combined DC/Dribble vaccine in treating mice with hepatic cancer, thus exploring their anti-tumor mechanisms.

METHODSDentritic cells were derived from Balb/c mice's spleen and their phenotypes were identified. Using hepatic cancer cell line BNL1MEA.7R.1 (abbreviated as BNL) originated from Balb/c mice as target cell, DC/Dribble vaccine was prepared via raising the antigen representing carrier autophagosomes (DRips in Blebs, DRibbles), which were rich in tumor antigen information. The mice previously immunized were divided into 4 groups, i.e., the control group, the beta-elemene group, the vaccine group, and the combined group. The PBS was subcutaneously and intraperitoneally injected to mice in the control group. The beta-elemene was intraperitoneally injected at the daily dose of 50 mg/kg to mice in the beta-elemene group and the combined group for 7 successive days. DC/Dribble vaccine was injected into the lymph node of mice in the vaccine group and the combined group on the 1st day, and DC/Dribble vaccine was subcutaneously injected on the 3rd day and the 5th day. All the mice were sacrificed on the 10th day. Their spleens were obtained sterilely, and the suspension was incubated with or without Dribble. The cells were inoculated for 72 h. The contents of IFN-gamma in the supernatant were measured by ELISA. In addition, the spleen cells obtained from the combined group were incubated with different stimulations for 72 h, which were then divided into the control group, the DRibble group, the DC group, and the DC/Dribble vaccine group. The supernatant of cultured cells were collected and the contents of IFN-gamma were measured by ELISA. The liver tumor-bearing mouse model was established, and then the BNL bearing mice were randomly divided into 4 groups, i.e., the control group, the beta-elemene group, the vaccine group, and the combined group. The treatment ways were the same as the immune ways. The tumor size and the survival period were observed in each group. On the 23rd day the mice were sacrificed. The tumor tissue was stripped and stained by HE staining. The pathomorphological manifestations of the tumor tissue were observed by light microscope.

RESULTSIn vitro detection of mice immunized previously by different ways showed that the secretion of IFN-gamma was significantly higher in the combined group than in the rest groups (P < 0.01). The secretion of IFN-gamma was significantly higher in the beta-elemene group and the vaccine group than in the control group (P < 0.01). The spleen cells could be stimulated to secrete a large amount of IFN-gamma in the vaccine group and the Dribble group (P < 0.01). When the beta-elemene was 10 microg/mL as the stimulating dose, the secretion of IFN-gamma obviously increased (P < 0.01). In vivo observation showed that the growth velocity of tumors in mice of the combined group was slowed down. There was statistical difference in the tumor area or the survival period of mice in the combined group, when compared with the other groups (P < 0.01). In HE staining, the surrounding connective tissues of the tumor were wrapped tightly and compactedly, with infiltration of a large amount of inflammatory cells.

CONCLUSIONSbeta-elemene combined DC/Dribble vaccine could induce specific immune cells to secrete secretory cells, thus exerting its anti-tumor effect. Its immunological effects might be associated with enhancing the DC antigen presenting function.

Animals ; Cancer Vaccines ; immunology ; Cell Line, Tumor ; Dendritic Cells ; drug effects ; immunology ; Female ; Liver Neoplasms ; drug therapy ; immunology ; Mice ; Mice, Inbred BALB C ; Sesquiterpenes ; pharmacology

OBJECTIVETo investigate the effect of Astragalus in regulating the imbalance between naive helper T cells (Th1/Th2) cytokines expression in patients with cervical cancer.

METHODSThirty patients with cervical cancer received intravenous dripping with 20 mL of Astragalus Injection (AI, contained extract from 40 g of crude drug) per day for 1 week, peripheral blood sample was collected from patients separately before and after treatment for extract mononuclear cells by density gradient centrifugation. The positive percentages of CD4+ interferon-gamma (IFN-gamma ) cell and CD4+ interleukin-4 (IL-4) cell in total CD4+ cells were measured by flow cytometry; the contents of IFN-gamma, IL-4 in culture supernate were detected with ELISA; and the expressions of T-cell transcription factor T-cells (T-bet) and GATA-binding protein-3 (GATA-3) were determined by RT-PCR. The data were controlled by those get from 10 healthy persons.

RESULTSCD4+ IFN-gamma positive cell percentage, T-bet mRNA expression level and concentration of IFN-gamma in supernate were significantly lower in patients than those in healthy control respectively, while CD4+ IL-4 positive percentage, level of GATA3 mRNA expression and IL-4 concentration in supernate were insignificantly different between the two groups. After AI treatment, the lowered parameters were up-regulated (P < 0.05), and no obvious change was observed in the CD4+ IL-4 positive cell associated parameters.

CONCLUSIONTh1/Th2 cell function imbalance existed in patients with cervical cancer, showing a Th2 predominant reaction mode; AI can regulate the imbalance, offset to Th1, thus to display its anti-tumor effect.

Aged ; Astragalus membranaceus ; chemistry ; Carcinoma, Squamous Cell ; drug therapy ; immunology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Interferon-gamma ; immunology ; Interleukin-4 ; immunology ; Middle Aged ; Phytotherapy ; Th1-Th2 Balance ; drug effects ; Uterine Cervical Neoplasms ; drug therapy ; immunology