Research on anti-tumor mechanism of attenuated Salmonella typhimurium VNP20009 / 药学学报

Attenuated Salmonella typhimurium VNP20009 is a widely used natural oncolytic bacterium, which has great application potential given its unique characteristics, including clinical safety, tumor targeting specificity, and explicit genome sequence. Here, we show that tumor progression can be effectively reduced by intraperitoneal administration with VNP20009 in a mouse model of melanoma (all animal experiments were conducted in accordance with the Animal Ethics Committee of China Pharmaceutical University); co-culture experiment in vitro demonstrated that VNP20009 can induce the polarization of macrophage M1, accompanied by expression of inflammation-related factors; flow cytometry analysis showed that VNP20009 induced the increase of immune cell infiltration in tumor. Further analysis showed that T cells infiltration in tumor-draining lymph node (TDLN) increased, and VNP20009 induced the activation of CD4+ T cells and CD8+ T cells in tumor. Our results demonstrate that VNP20009 treatment significantly inhibited melanoma tumors by remodeling tumor-associated macrophages to an M1-like phenotype, as well as recruiting and activating cytotoxic T cells, combined with its own antigenic activity to exert anti-tumor immunity.

Molecular mechanism of CD8+ T cell activation and differentiation / 中国免疫学杂志

CD8+ T cells play an essential role in defending against viruses,intracellular bacteria,protozoal infections and clearance of tumors since almost all the nucleated cells express MHCⅠ molecule.Following antigen recognition,CD8+ T cells are activated and differentiated to different subsets of effector or memory cells,which could clear the pathogen and form long-term protection.Phenotypic markers,functional properties and anatomical locations are different among these CD8+ T cell subsets.They also show variation in surviving time,proliferation and effector functions when re-challenged with the pathogen or tumor.Multiple signaling pathways and transcriptional factors are involved in CD8+ T cells activation and differentiation,and will be discussed in this review.We will also briefly summary the clinical applications of T cells against tumor or pathogens.

Clinical significance of detecting peripheral blood lymphocyte immunophenotype in patients with malignant carcinoma / 国际检验医学杂志

Objective To investigate the change of peripheral blood lymphocyte immunophenotype in the patients with malignant carcinoma and its clinical significance .Methods The flow cytometry was adopted to detect the expression levels of peripheral blood T lymphocyte subpopulations ,CD19+ cells ,CD3-CD56+ cells ,CD3+CD56+ cells in 167 patients with malignant carcinoma (inclu‐ding respiratory tract cancers ,gastrointestinal cancers and reproductive system cancer) and 170 normal controls as the healthy con‐trol group .The contrastive analysis was performed .Furthermore the analysis was conducted according to whether having tumor me‐tastasis and chemotherapeutic cycles .Results The total absolute value of the lymphocytes and the proportion of CD3+CD4+ cells in the patients with malignant carcinoma were significantly lower than those in the healthy control group (P<0 .05) ,but the propor‐tions of CD3+CD8+ ,CD3+CD56+ and CD3-CD56+ cells were significantly higher than those in the healthy control group (P<0 .05) .The proportion of CD3+CD4+ cells in the patients with tumor metastasis were significantly lower than those in the ones without tumor metastasis ;but the proportions of CD3+ CD8+ ,CD3-CD56+ and CD3+ CD56+ cells were significantly higher than those in the ones without tumor metastasis ,the differences were statistically significant(P<0 .05) .In the chemotherapy treatment , the proportions of CD3+CD4+ ,CD3+CD56+ and CD3-CD56+ cells were gradually increased with the increase of chemotherapeutic cycles ,but the proportion of CD3+CD8+ cells was gradually reduced .Conclusion In the process of development ,progression and treatment of tumor ,the cellular immunity function plays a dominant role ,which could be used as one of indexes for clinically moni‐toring the cellular immune function in the patients with tumor .

Effects of inhibitory and enhancing polypeptides from HCV core region on cytotoxic T cell functions / 第三军医大学学报

Objective To investigate the pathogenesis of cytotoxic T cell (CTL) dysfunction in patients with HCV infection. Methods CTL detecting system was established. Two polypeptides which could enhance CTL function and two polypeptides which could inhibit CTL function were selected and cross-combined. BALB/c mice were immunized by subcutaneous injection of the combined polypeptides, and the CTL activity in mouse spleen cells was detected by LDH release test. Results CTL activity in BLAB/c mice immunized by polypeptides in the core region of HCV could be enhanced by CPA10 (5-23 aa) and inhibited by CPA9 (39-74 aa). CTL activity in the mice could be enhanced by polypeptides from the HCV core region, CPB2+CPB8, and CPB6+CPB8, respectively. There was no obvious difference between CPB2+CPB7, CPB6+CPB7 and the negative control. Two-factor analysis of variance showed that there was reciprocal action between the inhibitory and enhancing polypeptides from the HCV core region. Conclusion CTL activity in BLAB/c mice can be detected stably by LDH. There is an interactive effect between the inhibitory and enhancing polypeptides from the HCV core region.

Histopathologic Features and Immunophenotype of 19 Primary Cutaneous Lymphomas

The diagnosis of primary cutaneous lymphoma is based on a combination of clinical, histological, immunophenotypic and genetic criteria. Nineteen cases of primary cutaneous lymphomas were studied for clinicopathologic, immunophenotypic, and genetic features. Seventeen (89%) cases were T cell origin and two cases (11%) were B cell origin. CD30-positive cutaneous lymphoproliferative disorder was the most frequent subtype, occupying 42% (8 cases) of the cases. CD8 was positive in 5 cases consisting of 3 cutaneous T cell lymphomas and 2 anaplastic large cell lymphomas. CD4 was positive in 2 cases of mycosis fungoides and 3 cases of lymphomatoid papulosis. Six (67%) of 9 cases of cutaneous T cell lymphoma were positive for TIA-1. Ten (83%) out of 12 cases showed clonal rearrangements of TCR gamma genes, however, one T/NK cell lymphoma and one anaplastic large cell lymphoma did not. EBV association was detected only in T/NK cell lymphomas among 10 cases examined. In conclusion, our study showed higher proportion of CD30-positive lymphoproliferative disorders and less frequent mycosis fungoides in Korea compared to the incidences in Western countries. Our immunostaining results suggested that mycosis fungoides and lymphomatoid papulosis are CD4-positive T cell origin, however, the remaining primary cutaneous T cell lymphoma is predominantly CD8-positive cytotoxic T cell origin.

Advances in study on pharmacological effects of polyactin / 中国药理学通报

This paper summarizes the recent 6～7 year advances in the research of pharmacological effects of polyactin including mainly six aspects: ①Effects of polyactin on functions of macrophages in vitro ; ② Mechanism enhancive effect ofpolyactin on NK cell activity; ③Effects of polyactin on the human lymphocyte immunofunction; ④Effects of polyactin on the proliferation and cytotoxicity of LAK; ⑤Enhances in specific antitumor activity in mice in vivo ; ⑥Effects of polyactin on erythrocyte deformability and immunofunction in Rabbit and Rat.

A study of the specific cytotoxic T cell of BALB/c mice detected by LDH / 第三军医大学学报

Objective To establish a simple animal model and the cytotoxic T cell(CTL) detecting system for the studies of the effects of CTL on HCV infection. Methods The CTL activity in BLAB/c mice immunized by polypeptides in the core region of HCV was detected with lactic dehydrogenase (LDH) by using SP2/O cells as the target cells. Results CTL activity in BLAB/c mice immunized by polypeptides in the core region of HCV could be detected with LDH. The activity could be enhanced by CPA10(5～23 aa) but inhibited by CPA9(39～74 aa). Conclusion CTL activity in BLAB/c mice can be detected stably by LDH.